Cancer treatment – Parentraide Cancer http://parentraide-cancer.org/ Tue, 11 Jan 2022 00:39:22 +0000 en-US hourly 1 https://wordpress.org/?v=5.8 https://parentraide-cancer.org/wp-content/uploads/2021/06/icon.png Cancer treatment – Parentraide Cancer http://parentraide-cancer.org/ 32 32 Researchers Shine Light on Molecular Landscape and Clinical Features of Rare Kidney Cancer https://parentraide-cancer.org/researchers-shine-light-on-molecular-landscape-and-clinical-features-of-rare-kidney-cancer/ Mon, 10 Jan 2022 23:38:00 +0000 https://parentraide-cancer.org/researchers-shine-light-on-molecular-landscape-and-clinical-features-of-rare-kidney-cancer/ Renal cell carcinoma with translocation (tRCC) is a rare and aggressive form of kidney cancer. It accounts for about 5 percent of all renal cell carcinomas in adults and about 50 percent in children. Relatively little is known about this cancer subtype, including its molecular basis and the best clinical treatment. In a new comprehensive […]]]>

Renal cell carcinoma with translocation (tRCC) is a rare and aggressive form of kidney cancer. It accounts for about 5 percent of all renal cell carcinomas in adults and about 50 percent in children. Relatively little is known about this cancer subtype, including its molecular basis and the best clinical treatment.

In a new comprehensive multicenter study of 152 samples, researchers at the Dana-Farber Brigham Cancer Center helped shed light on the molecular landscape and clinical features of the disease, finding that genetic alterations are rare in tRCC, with the exception of the fusion of genes from which it takes its name. . Their work further suggests that tRCCs may be sensitive to treatment with immune checkpoint inhibitors.

We believe that our findings concerning the potential of combinations of immunotherapies could be immediately exploitable in the clinic. Because this cancer is so rare, it is difficult to dedicate clinical trials to it. A thorough study of its molecular and clinical characteristics can help us develop a better roadmap for treatment. “

Ziad El Bakouny, MD, MSc, senior author, internal medicine resident, Brigham and Women’s Hospital

Source:

Journal reference:

Bakouny, Z., et al. (2022) Integrative clinical and molecular characterization of translocation renal carcinoma. Cell reports. doi.org/10.1016/j.celrep.2021.110190.

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Immunotherapy continues to affect all areas of lung cancer treatment https://parentraide-cancer.org/immunotherapy-continues-to-affect-all-areas-of-lung-cancer-treatment/ Sun, 09 Jan 2022 11:09:55 +0000 https://parentraide-cancer.org/immunotherapy-continues-to-affect-all-areas-of-lung-cancer-treatment/ Although trials such as phase 3 studies CheckMate 816 (NCT02998528) and POSEIDON (NCT03164616) are generating significant enthusiasm for the future of neoadjuvant therapy and combination chemoimmunotherapy, respectively, this is the phase trial 3 IMpower010 (NCT02486718) that made the most noise in non-small cell lung cancer (NSCLC), said David Spigel, MD. “[IMpower010] is the biggest essay […]]]>

Although trials such as phase 3 studies CheckMate 816 (NCT02998528) and POSEIDON (NCT03164616) are generating significant enthusiasm for the future of neoadjuvant therapy and combination chemoimmunotherapy, respectively, this is the phase trial 3 IMpower010 (NCT02486718) that made the most noise in non-small cell lung cancer (NSCLC), said David Spigel, MD.

“[IMpower010] is the biggest essay news because it led to a paradigm shift. Now we are talking about immunotherapy not only in advanced disease or unresectable stage III disease, but in a curable setting of resected disease, stage II and III, ”Spigel said in an interview with OncLive® during an Institutional Perspectives in Cancer webinar on lung cancer, which he co-chaired.

In the interview, Spigel, Scientific Director and Director of the Lung Cancer Research Program and Principal Investigator at the Sarah Cannon Research Institute, discussed the purpose of each presentation, which focused on immunotherapy versus chemo- Immunotherapy in the first-line metastatic setting, the surgical perspective of treatment in early-stage NSCLC, best practices for molecular testing and targeted EGFR and KRAS therapies for patients with advanced disease.

OncLive®: What developments have been made with regard to the first-line treatment for patients with advanced NSCLC without exploitable genetic alterations?

Spigel: We had several excellent presentations during the Institutional Perspectives in Cancer webinar. I focused on the state of play in the first line setting for NSCLC and where we are now with the immunotherapy and chemoimmunotherapy options in the first line setting. I focused on our non-TKI treatment options. We have a lot of diets to choose from [in this setting]. Cemiplimab-rwlc [Libtayo] is a new PD-1 inhibitor that has been approved by the FDA as first-line monotherapy based on the results of the EMPOWER-Lung1 trial [NCT03088540]. The study compared cemiplimab to platinum doublet chemotherapy in patients with 50% or greater PD-L1 expression. The results showed a survival advantage in the cemiplimab arm hence the FDA approval.

We now have 3 first-line monotherapies with pembrolizumab [Keytruda], atezolizumab [Tecentriq], and cemiplimab. Each agent is approved for patients with elevated PD-L1 expression, and pembrolizumab is also approved for patients with 1% to 49% PD-L1 expression.

In terms of chemotherapy combinations, the only novelty but not yet approved by the FDA is a design from the POSEIDON study. This was a trial that looked at a combination of dual immunotherapy and chemotherapy as the first-line treatment. In the trial, NSCLC patients with adenocarcinoma and squamous histologies were randomized to receive platinum doublet chemotherapy, platinum doublet chemotherapy with durvalumab [Imfinzi], which is a PD-L1 inhibitor, or platinum doublet chemotherapy with durvalumab and tremelimumab, which is a CTLA-4 antibody. The result here is that at ESMO 2021, we saw data presented by my partner, Melissa Johnson, MD, of the Sarah Cannon Research Institute, showing a survival advantage for the 4-drug regimen over the platinum doublet. Will this lead to the approval of this diet by the FDA? It looks like it should be, but we don’t have that approval yet.

Denis Gilmore, MD, of TriStar Medical Group, discussed the Phase 3 trials CheckMate 816 and IMpower010. What was the most exciting about these studies?

Dr Gilmore is a thoracic surgeon I have the privilege of working with in Nashville. Dr Gilmore did a fantastic job summarizing 2 pivotal studies from the past year: the CheckMate 816 study and the IMpower010 study. The CheckMate 816 study evaluated preoperative chemoimmunotherapy, in this case chemotherapy with nivolumab [Opdivo] in patients with squamous and non-squamous lung cancer that has been found to be resectable, hence stage 1B to stage IIIA. Study IMpower010 was an adjuvant trial, which evaluated patients with any histology of resected early stage lung cancer who received platinum doublet chemotherapy, if available. Then, the patients were randomized to receive or not receive aezolizumab adjuvanted at 1 year.

CheckMate 816 was essential because it showed that the rates of complete pathologic response are significantly higher, approximately ten times higher with chemoimmunotherapy compared to chemotherapy alone. Another interesting conclusion is that the operative results do not seem to be negatively impacted by the introduction of immunotherapy. In fact, there is a suggestion or statistical improvement in the ability to do less surgery, therefore smaller surgeries, minimally invasive surgeries, and no worse outcome with immunotherapy. It was a positive trial that has yet to lead to FDA approval. We recently saw a press release on disease free survival [DFS] improvements with the nivolumab arm, so hopefully this will lead to FDA approval.

The IMpower010 study recently led to FDA approval. Patients with resected stage II to IIIA NSCLC with 1% or greater PD-L1 expression are now candidates for immunotherapy, as in this study group there was an advantage of SSM in in favor of aezolizumab, which was the primary endpoint of the trial. Now there are a few caveats in that this benefit appears to be greatest or largely due to patients with 50% or greater expression, but approval is for patients with expression level PD-L1 of 1% or more. This is the biggest essay news because it has led to a paradigm shift. Now we are talking about immunotherapy not only in the case of advanced disease or unresectable stage III disease, but in a curable setting of resected disease, stage II and III.

Andrew Mackenzie, PhD, Sarah Cannon Research Institute, discussed biomarker testing. What mindset should be applied to molecular testing in the NSCLC?

Dr McKenzie leads our Personalized Medicine program at the Sarah Cannon Research Institute and is a fantastic colleague. I wouldn’t add much other than what everyone already enjoys, and that is the importance of testing. We certainly advocate for a large or full NGS [next-generation sequencing] testing in our patients with advanced disease, in this case advanced NSCLC. I don’t think it’s limited to adenocarcinoma; tests should be done in squamous cell carcinoma, if only to look for things like ENCOUNTER exon 14 [skipping mutations], which you can see in scaly histology and even rare things like RET and NTRK [alterations].

Ideally, the gold standard remains the fabric, but if you can only [test] one thing, get whatever can be done for you, and a lot of it turns into plasma testing. I recently met a woman with an advanced disease and [she and her family were] can’t wait to go [with treatment]. How do you make decisions based on someone who has a new diagnosis? You need to know their molecular results, and the fastest way to do that is through the plasma test. It has become a standard part of my work with patients as the tissue tests get ready, and with that, the PD-L1 tests.

Dr McKenzie gave a good summary of this landscape of tissue and blood-based testing, and they’re not going to go away. We don’t know much about its use and understanding the mechanisms of resistance or minimal residual disease, but these are exciting emerging areas for everyone and will likely become new standards in the years to come. For now, we just want to focus on performing the tests. There are so many markers, at least 8 that we want to know about in lung cancer. Knowing them will help guide the best treatment decisions for these patients.

Your co-chair, Melissa Johnson, MD, of the Sarah Cannon Research Institute, shared an overview of some of the more recently approved targeted therapies for patients with KRAS G12C mutations and EGFR exon 20 insertions. What has been learned about these agents in the clinic since their approval?

We are still talking about HER2, RET, and ROS alterations, and even sensitizing mutations in EGFR and what to do next [progression on standard therapy]. However, the important message from Dr Johnson was that we had obtained FDA approval in 2021 for the treatment of KRAS G12C mutant lung cancer with sotorasib [Lumakras], which is a TKI that selectively inhibits this genetic alteration, which can be found in plasma or tissue NGS tests. The agent is now approved for use in the refractory setting, so anything beyond first-line treatment, which is often based on chemoimmunotherapy.

Sotorasib now has FDA approval as an oral therapy for use in patients with KRAS G12C mutations, which is a testament to the importance of testing and getting answers in trying to be ready to use these therapies. We know that sotorasib is associated with response efficacy in approximately 40% to 50% of patients as well as prolonged durations of disease control that extend up to just under a year. Depending on the circumstances, some patients can go way beyond it, so it’s a big story.

Dr Johnson also spoke about another agent called adagrasib, which is an agent in development that also shows promise in the same patient population. It is not yet approved by the FDA, but hopefully it will be soon.

The other big story concerns patients with EGFR exon 20 insertions. These molecular alterations can be found with NGS tests, and we know about drugs like osimertinib [Tagrisso], which are ideal for patients with sensitizing mutations in exons 19 and 21 are not effective in exon 20 insertions although there has been some data with high dose osimertinib. The numbers are very low, but high dose osimertinib may be of benefit. We have 2 drugs approved by the FDA for patients with exon 20 insertions in EGFR: one is amivantamab-vmjw [Rybrevant], which is a bispecific antibody that targets EGFR and MET, then a TKI called mobocertinib [Ekivity], which is an oral agent. These 2 strategies approved by the FDA are respectively intravenous and oral, and are used in a post-first-line setting, therefore a refractory setting in patients with EGFR exon 20 insertions, much like the approval of sotorasib in KRAS G12C mutations.

These drugs are different; they are not the easiest to get used to administering. Amivantamab requires accelerated infusion, and in particular awareness of the management of infusion-related reactions, which occur in just about everyone, so we are adapting to this experience, including [that with] some pulmonary toxicity. Mobocertinib also has some unusual tolerability that doctors must get used to, whether it is gastrointestinal or pulmonary in nature. The big takeaway [message] is now we have 2 modifications, KRAS G12C and EGFR exon 20 insertions, for which a year ago we had no options. In terms of standards, we now have 3 and probably an option to come, which is exciting.


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Small Florida business got Covid therapy rarer than some large hospitals, raising questions of fairness https://parentraide-cancer.org/small-florida-business-got-covid-therapy-rarer-than-some-large-hospitals-raising-questions-of-fairness/ Sat, 08 Jan 2022 03:44:48 +0000 https://parentraide-cancer.org/small-florida-business-got-covid-therapy-rarer-than-some-large-hospitals-raising-questions-of-fairness/ TCovid-19 treatments, supported by the Florida Department of Health, came as a surprise: six large, mysterious boxes that showed up at Nicholas Suite’s iCare mobile medicine clinic near Miami on the morning of December 24. “We were wondering, what is this? Who sent us gifts? Has Santa Claus landed on the roof? ” he said. […]]]>

TCovid-19 treatments, supported by the Florida Department of Health, came as a surprise: six large, mysterious boxes that showed up at Nicholas Suite’s iCare mobile medicine clinic near Miami on the morning of December 24. “We were wondering, what is this? Who sent us gifts? Has Santa Claus landed on the roof? ” he said. “Then we opened it up and thought, ‘This is Evusheld! My God!'”

For some infectious disease physicians, this shipment has worrying implications. When they watched a government databaseSuite’s small private company appeared to have gotten more of the federal supply of this rare therapy than some of Florida’s major hospitals. In fact, iCare Mobile received enough for 264 courses – apparently the highest number the health department sent to any of the state providers on its first shipment from Evusheld.

Evusheld is a valuable substance, a cocktail of two monoclonal antibodies that can provide around six months of protection against Covid-19 for people who are too immunocompromised to mount a strong response to a vaccine, such as those who undergo chemotherapy or take immunosuppressive drugs afterwards. an organ transplant. The federal government distributed the small supplies it had to the states, which then sent them to medical centers.

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There is hardly enough for everyone who is eligible for therapy. The patients demanded it. Large teaching hospitals were ration it.

But here it was at iCare Mobile Medicine which Suite according to has six full-time staff: a paramedic, two paramedics, two paramedics, and himself, the only doctor. The company had gone out during the pandemic to make emergency home visits, dealing with issues such as burns and bouts of diarrhea, so the patient didn’t have to risk going to the hospital. . His services were often not covered by insurance, but paid for in cash or by credit card. The team then expanded to administering vaccines and therapies against Covid-19. Sometimes he’s been hired to set up a coronavirus testing table outside of private parties, Suite said, including those of the South Beach celebrity ensemble.

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“Anyone who doesn’t test negative doesn’t come in,” Suite said. “So we’re kind of like medical bouncers. “

Shortly after the surprise delivery, the clinic announced that it is also providing Evusheld injections – and the phones are ringing nonstop. The drug is free for patients, and although insurers could reimburse doctors to administer it, iCare’s priority was to get people injected, and is now working on billing. Insurance is not a requirement, Suite said.

Yet some infectious disease physicians fear that attempts to equitably distribute a rare drug to patients who would benefit most from it will be jeopardized if a portion of the doses goes to private companies that do not already care for patients. transplanted and cancerous.

“This raises really important questions about the fair and equitable attribution of this therapy,” said Michael Ison, professor in the divisions of infectious diseases and organ transplantation at Northwestern University Feinberg School of Medicine.

“If you think of the most effective way to provide patient protection with patient protection, everyone is on board at this point. But this must be weighed against real caution not to give it only to the people who are most financially able to obtain it. Otherwise, it flies in the face of the equitable distribution that hospitals are trying to do – and hopefully the state is trying to do, “said Cameron Wolfe, associate professor of medicine in the infectious disease division of Duke University, which chairs the university’s Covid-19 Therapeutics Committee.

He fears that different rationing systems in different places allow some people to bend the rules in ways others cannot. “People with resources find out where they are available and they go hunting. I got emails from folks in Ohio saying, “Hey, I see you got this medicine, can we drive over to Duke and buy some? “

But Duke doesn’t have enough of the monoclonal antibody cocktail for his own patients who would match the general criteria established by the Food and Drug Administration. Duke’s doctors treat thousands of immunocompromised people; their first Evusheld allocation consisted of around 300 doses. But there are different levels of immunosuppression, and Wolfe and his colleagues have taken that into account. An example of those who might be a priority to get Evusheld are patients whose cancer, transplantation, or autoimmune disease requires them to take drugs that have been clearly shown to inhibit the immune system’s response to vaccines.

Drugs like this “directly inhibit your body’s ability to make antibodies.” This is how they are designed. And so people don’t make antibodies against vaccines, ”Wolfe said, adding that this is not necessarily true for everyone who has had a kidney transplant or is undergoing chemotherapy.

At iCare Mobile Medicine, on the other hand, the criteria for this prophylactic treatment are less stringent than those of Duke and other similar centers. Instead, these are the more general ones stated by the FDA. If you’re immunocompromised, don’t have Covid-19, and live in Florida at least part of the year, Suite explained, then you can get Evusheld. “We don’t sort people out and say, ‘Well, you look really sick or you are really old.’ We follow the criteria that the government and the manufacturer have set and it really comes down to being first come, first served. “

Finding a fair distribution system is complex. Some doctors find it ethically questionable for people who can afford the trip to become Evusheld tourists, although in some cases patients may be in the priority category even if they live within a few states of their center. transplantation and can therefore travel without taking the plunge. well thought out line. “We realized this because at least two of our patients here in Illinois went to Florida to this private clinic to get Evusheld,” Northwestern doctor Ison said, referring to iCare.

Suite said his clinic does not give the drug to permanent residents of other states, although it does provide it to snowbirds who live part of the year in Florida and part of the year elsewhere. He and his colleagues had been harassing the state’s health department so they could get Covid vaccines for patients they saw in their homes, and they were successful. This laid the groundwork for their request for Evusheld, Suite said. “Our name was well known in the health department: ‘Oh, yeah, these guys really bother us a lot. They want things to help their patients. They were surprised they received some of the prophylaxis, but thrilled that they could help retirees in South Florida, many of whom have had cancer or transplants.

Suite agrees that giving top priority to the most vulnerable patients is vital, but it is not clear whether large university-affiliated hospitals are necessarily the best or only way to ensure equitable access. “The only constant stream of concern that I perceived was that there are a lot of oncologists and community physicians who do transplants outside of the major university centers,” he said. Their patients, he continued, “are traditionally marginalized by these same academic medical centers.”

Many hospitals, Suite said, were refusing to give Evusheld to patients who were not already receiving treatment from them, as well as to some who were, and iCare became an alternative. “We have patients from Orlando, Daytona Beach, the west coast of Florida like Tampa for example: people who were already receiving treatment for their transplant or for their cancer in large centers in the state of Florida , but they could not even enter their own establishment. Because there just wasn’t enough supply, ”he said.

It is not known how the Florida Department of Health chose to allocate doses to different institutions – it did not respond to requests for comment by email and phone. Ison and Wolfe see the point of Suite. After all, being able to get cancer treatment or a transplant in some hospitals is often a privilege. They just want to make sure that these gaps are not further compounded in the distribution of a scarce resource.

“Giving [Evusheld] to this type of concierge services for distribution could potentially be justified to facilitate access to medicines, ”Ison said. But he wondered why not donate some to transplant or oncology clinics that may not have one at all, given that their lists are already full of eligible patients.

“There will certainly be people who will not be well served by academic medical centers. I couldn’t agree more, ”said Wolfe. “Therefore, why do I think: What is the optimal distribution? It’s the one where we’re all kind of on the same page as to who really needs it the most. It should be independent of where you see your doctor.


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The shadow of cancer on fertility https://parentraide-cancer.org/the-shadow-of-cancer-on-fertility/ Wed, 05 Jan 2022 00:30:00 +0000 https://parentraide-cancer.org/the-shadow-of-cancer-on-fertility/ By Kalwyna Rathod If the treatment involves radiation therapy, the ovaries will be exposed to high-energy rays, which can damage them. Cervical cancer can impact a woman’s chances of getting pregnant, because cancer treatments pose a risk to fertility. However, preserving fertility during cancer treatments is now a possibility, says Dr Indhumathi Joy Dinakar, Consultant […]]]>
By Kalwyna Rathod

If the treatment involves radiation therapy, the ovaries will be exposed to high-energy rays, which can damage them.

Cervical cancer can impact a woman’s chances of getting pregnant, because cancer treatments pose a risk to fertility. However, preserving fertility during cancer treatments is now a possibility, says Dr Indhumathi Joy Dinakar, Consultant and Fertility Expert, Nova IVF. “Infertility depends on many factors, such as the stage of the cancer, the time of diagnosis, the time remaining until the start of treatment and the treatment plan. There are a few options that may be helpful for women looking to preserve their fertility, before embarking on treatment, ”she adds.

Cancer of the cervix, mainly due to Human papillomavirus Where HPV (which women can now be vaccinated against), is a type of cancer that starts in cells in the cervix, the lower part of the uterus, and in the uterus. Cervical cancer can affect the deeper tissues of the cervix and can spread to other parts as well.


Fertility and cervical cancer

Some methods of treating cervical cancer can reduce your chances of getting pregnant. Dr Dinakar says, “If cervical cancer is not diagnosed early, there is a good chance that a radial hysterectomy will need to be performed, resulting in the removal of the uterus or uterus from the body. In this case, the patient will no longer be able to bear a child in the future. This is also true if the ovaries are removed, as the patient will not be able to produce eggs. ”

Also, if your treatment involves radiation therapy, your ovaries will be exposed to high-energy rays, which can damage them. “This will lead to infertility because some eggs will be destroyed, causing early menopause. In addition, women who undergo radiation therapy face a high risk of miscarriage or premature labor because the uterus is exposed to radiation, ”says Dr Dinakar. Additionally, some chemotherapy drugs can also impact the ovaries and uterus, leading to early menopause.

Preserving fertility

Before undergoing any treatment, the medical advice of the doctor / fertility specialist should be taken into account.

Conization

A conical biopsy is done at the very beginning of cancer when there is a small growth in the cervix. The doctor will remove the cone-shaped area of ​​the cervix or the cancerous tissue. This treatment does not completely cause infertility, although there is a small risk of preterm delivery and low birth weight. The patient should wait a period of at least 8 to 12 months before planning a pregnancy to discuss the risk of miscarriage involved.

Radical trachelectomy

As part of this procedure, the doctor will remove the signs of small tumors in the early stages of cervical cancer by removing most of the cervix, the upper part of the vagina, and the lymph nodes. The doctor will prick the inner part of the cervix. Dr Dinakar says: “There is a good chance of conceiving after this procedure. Due to the permanent point in the cervix, the baby can only be delivered by cesarean section. Pregnancy will be at high risk given the risks of miscarriage and premature delivery, requiring the supervision of a gynecologist.

For chemotherapy and hysterectomy

If the doctor recommends radiation therapy, chemotherapy, or a hysterectomy, the patient may consider freezing her eggs. One should consult a fertility expert to understand the risks and benefits of egg freezing. Note that radiation therapy and chemotherapy can damage the uterus and the ovaries, therefore, the patient will not be able to carry a child in the womb. With egg freezing, one can conceive of in vitro fertilization (IVF) or consider finding a surrogate mother. You should consider becoming pregnant a few months after the end of cancer treatment.

Coping with cervical cancer and infertility

Cancer in itself is a huge problem to be treated. It destroys and damages a person both physically and emotionally. “The infertility associated with cervical cancer can be emotionally draining for both partners. But research and studies have given women with cervical cancer the ability to choose other methods of conception. Before giving up hope, see your doctor and a fertility specialist, who can guide you through your treatment and your chances of conceiving, ”explains Dr Dinakar.


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Cantargia Advances Nadunolimab In Pancreatic Cancer In PanCAN Precision PromiseSM Phase 2/3 Clinical Trial https://parentraide-cancer.org/cantargia-advances-nadunolimab-in-pancreatic-cancer-in-pancan-precision-promisesm-phase-2-3-clinical-trial/ Mon, 03 Jan 2022 08:04:19 +0000 https://parentraide-cancer.org/cantargia-advances-nadunolimab-in-pancreatic-cancer-in-pancan-precision-promisesm-phase-2-3-clinical-trial/ STOCKHOLM, January 3, 2022 / PRNewswire / – Cantargia AB today announced that the Pancreatic Cancer Action Network (PanCAN) Precision PromiseSM The Phase 2/3 clinical trial, conducted at leading clinical centers in the United States, plans to include nadunolimab in combination with chemotherapy as an investigational first-line treatment in metastatic pancreatic cancer (PDAC). The trial […]]]>

STOCKHOLM, January 3, 2022 / PRNewswire / – Cantargia AB today announced that the Pancreatic Cancer Action Network (PanCAN) Precision PromiseSM The Phase 2/3 clinical trial, conducted at leading clinical centers in the United States, plans to include nadunolimab in combination with chemotherapy as an investigational first-line treatment in metastatic pancreatic cancer (PDAC). The trial uses a Bayesian platform designed by PanCAN in collaboration with the United States Food and Drug Administration (FDA) to provide a basis for market approval of therapies in PDAC. The primary endpoint of the trial is overall survival. PanCAN’s plan is to submit a pre-IND application to the FDA in the second quarter of 2022 to include the nadunolimab treatment arm as an experimental arm in Precision Promise.

With the positive data obtained with nadunolimab in pancreatic cancer, we are proud to have been selected to advance development in collaboration with PanCAN and its strong clinical network. Cantargia’s goal is to provide new treatment options for patients with life-threatening diseases. The study of nadunolimab in Precision Promise fits well with our strategies,“said Göran Forsberg, CEO of Cantargia.

The interleukin-1 receptor accessory protein binding antibody (IL1RAP) nadunolimab is Cantargia’s flagship program and is the subject of five clinical trials evaluating combination regimens in various forms of cancer, with PDAC being the most studied. To date, more than 70 PDAC patients have received treatment with nadunolimab in combination with gemcitabine and nab-paclitaxel in the CANFOUR phase 1 / 2a clinical study. Interim results of 33 PDAC patients, presented at the ESMO congress in September 2021 and updated in december 2021, show that median progression-free survival (iPFS) and overall survival are longer than expected for chemotherapy alone, based on historical control data.

Cantargia has considered several opportunities to advance the clinical development of nadunolimab in PDAC and today announces the decision to participate in PanCAN’s Phase 2/3 adaptive clinical trial, Precision Promise. In addition to advancing the clinical development of PDAC, ongoing activities for nadunolimab in non-small cell lung cancer will continue as planned with the goal of starting a randomized clinical study in late 2022.

PanCAN’s Precision Promise adaptive clinical trials platform is currently being conducted in the United States at 15 leading clinical centers, with additional sites added as the trial progresses. In the trial, patients will be randomized to receive an investigational treatment with nadunolimab plus gemcitabine and nab-paclitaxel, or a standard chemotherapy regimen alone. In addition, consistent with the platform nature of Precision Promise, other experimental arms will be evaluated simultaneously with the nadunolimab arm. The design of the Bayesian trial is to enroll up to 175 patients in each experimental arm while randomizing patients into the standard care control arms. Depending on the results of the arm at that time, the success of a stage 1 of the adaptively randomized trial in 100 patients can be followed seamlessly by a transition to a fixed randomized stage 2 in 75 patients. If a transition to stage 2 of the nadunolimab arm occurs, recruitment will continue without any announcement of the trial results until the final analysis of the comparison of the arm with the control. Trial results for the nadunolimab arm are expected to be available in or before 2027.

Prior to the start of treatment of patients in the nadunolimab arm, additional meetings with regulatory authorities will take place, followed by the regulatory submission of a pre-IND for this investigational arm. The pre-IND is expected to be submitted to the US FDA in the second quarter of 2022. Cantargia will fund the nadunolimab business and be responsible for the supply of the drug.

The goal of PanCAN’s precision promise is to accelerate drug development and bring new pancreatic cancer therapies to patients faster,“said Anne-Marie Duliege, MD, medical director of PanCAN.”It is important that we continue to partner with innovative pharmaceutical companies to expand the investigational treatments studied in this trial and we look forward to working with Cantargia to incorporate nadunolimab into Precision Promise.

You can find more information about PanCAN, Precision Promise and participating centers at https://www.pancan.org/research/precision-promise/ and on https://clinicaltrials.gov/ct2/show/NCT04229004.

For more information, please contact

Göran Forsberg, CEO

Telephone: +46 (0) 46-275 62 60

Email: goran.forsberg@cantargia.com

This is information that Cantargia AB is obliged to make public in accordance with the EU Market Abuse Regulation. The information was submitted for publication, through the contact person indicated above, at 8:30 a.m. CET on January 3, 2022.

About Cantargia

Cantargia AB (publ), reg. no. 556791-6019, is a biotechnology company that develops antibody-based treatments for life-threatening diseases and has established a platform based on the IL1RAP protein, implicated in a number of forms of cancer and inflammatory diseases. The main project, the nadunolimab antibody (CAN04), is being studied clinically in combination with chemotherapy or immune therapy with a primary focus on non-small cell lung cancer and pancreatic cancer. Intermediate positive data from the combination with chemotherapy indicate greater efficacy than expected from chemotherapy alone. Cantargia’s second project, the CAN10 antibody, focuses on the treatment of severe autoimmune / inflammatory diseases, initially focusing on systemic sclerosis and myocarditis.

Cantargia is listed on Nasdaq Stockholm (ticker: CANTA). More information about Cantargia is available at www.cantargia.com.

About nadunolimab (CAN04)

The CAN04 antibody binds tightly to its IL1RAP target and functions by inducing ADCC and blocking IL-1α and IL-1β signaling. Thus, CAN04 may counteract the contribution of the IL-1 system to the immunosuppressive tumor microenvironment and the development of resistance to chemotherapy. CAN04 is being studied in several ongoing clinical trials. In the CANFOUR phase I / IIa study, first-line combination therapy is being studied with standard chemotherapies in patients with PDAC (gemcitabine / nab-paclitaxel) and patients with NSCLC (cisplatin / gemcitabine) (NCT03267316). Intermediate positive data for combination therapies show durable responses or pseudo-progression in patients with PDAC, resulting in a median iPFS of 7.2 months and a median survival of 12.7 months. Higher efficacy was also seen in patients with NSCLC with a median PFS of 7.2 months. A response rate of 53% was observed in patients with non-squamous NSCLC, with even higher responses in patients previously treated with pembrolizumab. These results show greater efficacy than that expected from chemotherapy alone. CAN04 is being studied with chemotherapy also in the phase I CAPAFOUR study, with the FOLFIRINOX regimen for the first-line treatment of metastatic PDAC (NCT04990037) and in two other clinical studies, CESTAFOUR and TRIFOUR, in other forms of cancer, including cancer of the biliary tract, colorectal cancer and triple negative breast cancer. CAN04 is also being evaluated with the immune checkpoint inhibitor pembrolizumab, with or without chemotherapy, in the phase I study CIRIFOUR (NCT04452214).

About PanCAN and Precision PromiseSM

The Pancreatic Cancer Action Network (PanCAN) is leading the way in accelerating critical progress for pancreatic cancer patients. PanCAN is taking bold action by funding vital research, delivering personalized patient services and creating a community of supporters and volunteers who will stop at nothing to create a world in which all pancreatic cancer patients will thrive . PanCAN’s promise of precisionSM is a Phase 2/3 clinical trial platform and contains an adaptive design for the parallel evaluation of several new treatments for pancreatic cancer. It serves as a catalyst to accelerate the development of pancreatic cancer drugs, reduce the risks of industry participation, increase clinical trial registrations, and transform the way clinical research is done for patients with pancreatic cancer. .

This information was brought to you by Cision http://news.cision.com

https://news.cision.com/cantargia-ab/r/cantargia-advances-nadunolimab-against-pancreatic-cancer-in-the-pancan-precision-promise-sm–phase-2,c3480557

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Ron DeSantis accompanied his wife to cancer treatment as critics claimed he was ‘missing’ https://parentraide-cancer.org/ron-desantis-accompanied-his-wife-to-cancer-treatment-as-critics-claimed-he-was-missing/ Sat, 01 Jan 2022 16:12:47 +0000 https://parentraide-cancer.org/ron-desantis-accompanied-his-wife-to-cancer-treatment-as-critics-claimed-he-was-missing/ TALLAHASSEE, Florida – Florida Republican Gov. Ron DeSantis accompanied his wife to her cancer treatment as critics accused the governor of taking vacation as coronavirus cases increased, Fox News has learned. A spokesperson for DeSantis said the governor accompanied his wife Casey for cancer treatment on December 29, the day several left-wing critics accused the […]]]>

Florida Republican Gov. Ron DeSantis accompanied his wife to her cancer treatment as critics accused the governor of taking vacation as coronavirus cases increased, Fox News has learned.

A spokesperson for DeSantis said the governor accompanied his wife Casey for cancer treatment on December 29, the day several left-wing critics accused the governor of “disappearance.”

DeSantis announcement in October that his wife was diagnosed with breast cancer, telling Fox News at the time that as “a mother of three young children, Casey is the centerpiece of our family and has had an impact on life countless Floridians thanks to her initiatives as first lady. “

THE DESANTIS OFFICE FOUND AFTER THE MAYOR ASKS “WHERE IS OUR GOVERNOR?” “

Democratic Mayor Jerry Demings of Orange County in Florida slammed DeSantis at a press conference on Tuesday amid the surge COVID case, suggesting that residents of the state “should be outraged” with DeSantis not being in front of the media during the peak.

“Our residents, all Florida residents should be outraged, and they should ask the question, ‘Now where is our state? Where is our governor?’” Demings noted. “Where is Ron DeSantis now?” When was the last time you saw the governor give a media availability regarding COVID-19? “

Others, including Rep. Alexandria Ocasio-Cortez, DN.Y., have taken to social media to criticize DeSantis and accuse him of being “inexplicably missing.”

“Hasn’t Governor DeSantis been inexplicably missing for about 2 weeks,” Ocasio-Cortez wrote in a tweet during a visit to Florida. “If he’s here, I’d be happy to say hello to him. His social media team seems to have posted old photos for weeks.”

“In the meantime, maybe I could help with the local organization,” added Ocasio-Cortez, who was spotted without mask while drinking and dining outside in the Sunshine State. “People are quite receptive here.”

MSNBC host Joy Reid also lashed out at DeSantis, writing in a tweet: “A governor, who doesn’t govern during a crisis, and instead takes the sun on vacation. @GovRonDeSantis is Ted’s Nero Cruzes. “

DeSantis press secretary Christina Pushaw responded to Reid, attaching photos from DeSantis’ daily schedule, and asked, “Did you ever think you were one of the reasons why nobody trusts the media?

DeSantis communications staff member Kyle Lamb also responded to critics on Twitter who wondered if DeSantis was on vacation, writing: “Just for the record, [DeSantis] is not on vacation. Literally no one in our office said it was.

CLICK HERE TO GET THE FOX NEWS APP

“Anyone pushing who could have easily seen the public schedule and saw that he was taking calls and meetings last week,” Lamb added. “Not holding public events does not mean = ‘vacation’. “

Read more on FOXNews.com.



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Leonhardt Ventures files patent for bioelectric diabetes reversal treatment via FABp4 regulation and Klotho regulation https://parentraide-cancer.org/leonhardt-ventures-files-patent-for-bioelectric-diabetes-reversal-treatment-via-fabp4-regulation-and-klotho-regulation/ Fri, 31 Dec 2021 03:19:58 +0000 https://parentraide-cancer.org/leonhardt-ventures-files-patent-for-bioelectric-diabetes-reversal-treatment-via-fabp4-regulation-and-klotho-regulation/ Mission Viejo, California, United States, December 30, 2021 (GLOBE NEWSWIRE) – Leonhardt Ventures LLC today announced the filing of a patent application covering the controlled bioelectric down-regulation of FABp4 and up-regulation of klotho with the potential aim of reversing types 1 and 2 diabetes. Published studies have documented that serum FABp4 levels are higher in […]]]>

Mission Viejo, California, United States, December 30, 2021 (GLOBE NEWSWIRE) – Leonhardt Ventures LLC today announced the filing of a patent application covering the controlled bioelectric down-regulation of FABp4 and up-regulation of klotho with the potential aim of reversing types 1 and 2 diabetes.

Published studies have documented that serum FABp4 levels are higher in patients with type 2 diabetes than in healthy individuals and that klotho levels are lower. Overexpression of FABp4 interferes with the ability of the pancreas and beta cells to produce healthy insulin levels. Klotho deficiency leads to decreased insulin production and increased insulin sensitivity.

Other studies have shown a correlation between abnormally low levels of FABp4 and type 1 diabetes. In these patients, moderately controlled regulatory control to return to normal, but not higher, levels may be helpful.

This new patent filing is based on the hypothesis that inhibition of FABP4 will attenuate intracellular lipid content and improve insulin signaling and insulin-stimulated glucose uptake, thus potentially reversing the effects of diabetes mellitus. type 2. Klotho supplementation increases insulin production and improves insulin sensitivity to return to normal levels (needs to be studied in well-controlled statistically significant clinical trials to prove this).

In 2017, around 462 million people were affected by type 2 diabetes, corresponding to 6.28% of the world’s population (4.4% of people aged 15-49, 15% of people aged 50 at 69 years and 22% of people aged 70 and over), for a prevalence rate of 6,059 cases per 100,000. More than one million deaths per year can be attributed to diabetes alone, making it the ninth cause of death. The burden of diabetes mellitus is increasing globally, and at a much faster rate in developed regions, such as Western Europe. The distribution between the sexes is even and the incidence peaks at around age 55. The global prevalence of type 2 diabetes is projected to increase to 7,079 people per 100,000 by 2030, reflecting a continued increase in all regions of the world. There are worrying trends of increasing prevalence in low-income countries. Urgent research in public health, clinical prevention and accelerated treatment is warranted and the Leonhardt Ventures team is committed to making its contribution.

“The bioelectrically controlled down-regulation of FABp4 and the up-regulation of Klotho could potentially be a major breakthrough in the treatment of diabetes. This technology deserves further examination and study. Says Dr. Leslie Miller, Chief Medical Officer, Leonhardt Ventures LLC, PancreaCell LTP and Leonhardt’s Launchpads Accelerator.

Leonhardt Ventures LLC has issued, pending, pending, electing or licensed over 800 patent applications related to organ regeneration, healing and recovery. https://patents.justia.com/inventor/howard-j-leonhardt.

The Leonhardt patent and pending patents include patent claims for klotho expressing MSCs, a circulating-controlled bioelectric regulation of klotho https://patents.justia.com/patent/20200289826, bioelectric stem cell research, proliferation and differentiation control, bioelectric personalized inflammation control, bioelectric cancer treatment (10 U.S. patents issued), and bioelectric and biological organ regeneration, including pancreatic regeneration.

PancreaCell LTP a formative step The startup Leonhardt Ventures LLC has been working for years on perfecting the regeneration of the pancreas –

https://player.vimeo.com/video/170533425?h=74e8cc5cde

Another recently published study linked low klotho levels to pancreatic cancer – https://www.mdpi.com/2072-6694/13/24/6297

The Leonhardt team has already issued 10 US patents for the bioelectric treatment of cancer, including the treatment of pancreatic cancer, and has many other cancer-related patent applications pending at the USPTO, including those for modulation. klotho.

In clinical studies in Brazil, researchers sponsored by Leonhardt Ventures demonstrated an ability to increase circulating klotho by 150% in patients with kidney failure with just a few short stimulation sessions per week for 8 weeks. In our own R&D laboratories as part of preclinical studies, we obtained increased cell and tissue expressions of> 480%.

The Leonhardt team working with the startup BioLeonhardt Whole Body is developing the BodStim www.bodstim.com Stimulation combination designed to increase circulating klotho levels that are in the early stages of clinical OUS evaluation.

KlothoBios, another startup from Leonhardt Ventures, unveiled the Klotho years Klotho Blood Test – www.klothoyears.com The team working with established testing partners have successfully completed 20 test runs of this Klotho level testing system and methods and are preparing for a larger clinical study.

About Leonhardt Ventures LLC: Since 1982, the Leonhardt team has been developing and implementing medical devices and biotechnological inventions. Over 600,000 patients have been treated with Leonhardt’s inventions to date. See www.leonhardtventures.com for more information.

About PancreaCell LTP: PancreaCell is a forming-stage startup of Leonhardt Ventures LLC focused on regenerating the pancreas with a convergence of bioelectrical and biological products.

About Leonhardt Launchpads: Leonhardt’s Launchpads, founded in 2008, is the innovation and startup launch accelerator arm of Leonhardt Ventures LLC, which aims to help accelerate the development of innovation in bioelectric, biological and endovascular technologies through early studies on the man.

About CancerCell LTP: CancerCell is an early stage Leonhardt Ventures LLC startup focused on bioelectric and biological treatments for cancer, including pancreatic cancer. They have ten (10) issued patents for the treatment of bioelectric cancer and dozens of other patent applications pending with the USPTO at present. See www.cancercellinc.com

Warnings and Disclaimers: The product is not yet proven safe or effective. Forward-looking statements are subject to change without notice. Patents granted may be invalidated. Patents pending cannot be granted. Optional or licensed patents may not be maintained. The company, via an accelerator business model, shares resources in all forms between several entities. The company lacks sufficient resources to bring the products through clinical studies and to market. The company uses off-the-shelf devices and components to speed up development time where possible. Timelines are subject to change even from year or decade to decade. The company tries to do in organ regeneration what no other company or organization, even those with substantially higher resources, has ever been able to do. As an investment, this should be considered in the highest risk category for a total loss. Statistics on innovation and startup accelerators around the world indicate a blockbuster success rate of around 4% among portfolio startup entries in the top of the top accelerators. The company has a small workforce to manage over 50 websites with over 10,000 pages of documents, and it is highly likely that some pages will contain outdated information at some point. If you have specific questions, please email us for the most recent information. Priorities are constantly changing and resources are reallocated by the business design based on the acquisition interest expressed by potential buyers / strategic partners and other opportunity drivers.

Contact: Brian Hardy, Marketing Director, Email brian_fizzpopmedia@customers.prdistribution.org for more information.

For the original report, please visit https://prdistribution.com/news/leonhardt-ventures-files-patent-for-bioelectric-diabetes-reversal-treatment-via-fabp4-regulation-and-klotho-regulation.html


Media Company: Leonhardt Ventures LLC - PancreaCell LTP, 
Media Name: Howard J. Leonhardt, 
Media Phone: (424) 291-2133, 
Media Email: howard@leonhardtventures.com
Media URL: http://www.leonhardtventures.com/

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More affirmation of the benefits of ambulatory palliative care in terminal cancer https://parentraide-cancer.org/more-affirmation-of-the-benefits-of-ambulatory-palliative-care-in-terminal-cancer/ Wed, 29 Dec 2021 22:00:20 +0000 https://parentraide-cancer.org/more-affirmation-of-the-benefits-of-ambulatory-palliative-care-in-terminal-cancer/ Most end-stage cancer patients did not receive outpatient palliative care, despite their association with reduced hospitalizations and increased use of palliative care, a retrospective analysis showed. Overall, 50% of 522 patients received palliative care, which was linked to greater use of palliative care, do not resuscitate (DNR) designation, and advanced planning, at some point before […]]]>

Most end-stage cancer patients did not receive outpatient palliative care, despite their association with reduced hospitalizations and increased use of palliative care, a retrospective analysis showed.

Overall, 50% of 522 patients received palliative care, which was linked to greater use of palliative care, do not resuscitate (DNR) designation, and advanced planning, at some point before the death. However, only one in five patients has been exposed to outpatient palliative care.

Palliative inpatient care was associated with increased length of hospital stay. In contrast, outpatient palliative care dramatically reduced hospitalizations and end-of-life intensive care (EOL) and dramatically increased the length of hospice stay, reported Jonathan C. Yeh, MD, of Beth Israel Deaconess Medical Center and from Harvard Medical School in Boston, and co-authors in JCO oncology practice.

“Our results suggest that palliative care is associated with better quality end-of-life care, but inpatient and outpatient palliative care have different effects,” the authors concluded. “Patients with advanced cancer should receive outpatient palliative care early, along with cancer treatment. The expansion and strong support of ambulatory palliative care should be a priority for hospitals. “

The study added to a “robust” evidence base supporting the benefits of ambulatory palliative care for cancer patients, said Neha Kayastha, MD, and Thomas W. LeBlanc, MD, of the Duke Cancer Institute in Durham. , in North Carolina, in a accompanying editorial. Over the past decade, nearly a dozen randomized clinical trials have demonstrated the benefits of ambulatory palliative care, and several systematic reviews and meta-analyzes have confirmed the benefits.

“However, despite this clear evidence, we have failed to implement large-scale palliative care outside of trials,” they wrote.

Kayastha and LeBlanc cited multiple barriers to integrating palliative oncology care. Lack of clinician awareness of available services, lack of patient awareness of the potential benefits of hospice care, and lack of resources for hospice clinics all contribute to the problem.

“The current model of integrating palliative care relies on oncologists to recognize unmet needs and then refer patients and is therefore doomed to failure due to an incomplete understanding of palliative care and its benefits,” said noted Kayastha and LeBlanc. “A better system would trigger referrals based on standard criteria through objective assessments of unmet needs.”

“It is tragic that despite more than a decade of evidence and recommendations from society, we still fail to deliver what we know to be a meaningful service to patients and families. We need to do better,” they concluded.

When planning the scan, Yeh and his colleagues assumed that palliative care improves outcomes in advanced cancer. Noting that most palliative care takes place in hospital settings, they sought to quantify exposure to inpatient and outpatient palliative care and to describe associations between palliative care and end-of-life quality measures.

The analysis included 522 patients who were admitted to an inpatient oncology unit from October 1, 2017 to September 30, 2018. Follow-up continued until October 1, 2020, when all patients had died. . The study population had a median age of 69 years at the time of death, males accounted for 53% of the total, 25% of patients identified as racial or ethnic minorities, and 82% had advanced or metastatic solid tumors.

Medical records showed that 259 patients (50%) had some exposure to palliative care, including 111 patients who had been exposed to outpatient palliative care (42% of all palliative care and 21% of the total study population ). Patients who received inpatient palliative care had a median of five visits, the first occurring a median of 45 days before death. Patients exposed to outpatient palliative care had a median of two visits, the first occurring a median of 223 days before death.

In all patients, the most common reasons for hospitalization were complications from the cancer or treatment, such as infection, uncontrolled symptoms, or factors associated with disease progression. Patients who received palliative care were younger (66 vs 71; P<0.001) and more likely to be female (52% vs. 42%; P= 0.03).

Overall, palliative care was associated with longer hospital stay (8.4 versus 7.2 days; P= 0.03), but the subgroup analysis showed that the difference was due to a longer length of stay in patients who received only inpatient palliative care. Patients who were exposed to outpatient palliative care spent an average of 6.3 days in hospital compared to 8.2 days for patients who had no palliative care visits (P<0.001), as well as significantly fewer total hospital days for the entire year (16.0 vs. 21.2; P= 0.003).

Patients exposed to palliative care were more likely to enroll in palliative care (78% vs. 44%; P<0.001), although the length of stay in hospice does not differ. Again, the subgroup analysis showed that patients exposed to outpatient palliative care had significantly longer hospice stays (46.5 versus 27.1 days for all others; P= 0.002).

Palliative care had a significant association with documentation of advanced care planning in electronic health records (53% vs. 31%; P<0.001) and status of the DNR code at the time of death (87% versus 55%; P<0.001). Patients exposed to palliative care were more likely to die at home or in palliative care, and the subgroup exposed to outpatient palliative care was less likely to receive intensive care unit care in the last 30 days of life (6 % against 15%; P= 0.046).

  • Charles Bankhead is Editor-in-Chief for Oncology and also covers Urology, Dermatology and Ophthalmology. He joined MedPage Today in 2007. To follow

Disclosures

Yeh has revealed a relationship with Takeda.

LeBlanc disclosed relationships with AbbVie, Astellas Pharma, Seattle Genetics, Pfizer, Genentech, AstraZeneca, Daiichi Sankyo, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Agios and Jazz Pharmaceuticals, as well as patent / royalty / intellectual property interests.



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New approach to target activator-dependent cancers – Potential therapeutic approach for over 90% of prostate cancers https://parentraide-cancer.org/new-approach-to-target-activator-dependent-cancers-potential-therapeutic-approach-for-over-90-of-prostate-cancers/ Tue, 28 Dec 2021 12:11:19 +0000 https://parentraide-cancer.org/new-approach-to-target-activator-dependent-cancers-potential-therapeutic-approach-for-over-90-of-prostate-cancers/ Foreground: SWI / SNF allows oncogenic transcription. Background: SWI / SNF is the inactivated deactivation of oncogenic transcription. Credit: Ella Maru Studio Chromatin degradation prevents transcription factors from causing cancer, which may be a potential therapeutic approach for over 90% of prostate cancers. As researchers have identified several genes responsible for prostate cancer, a new […]]]>

Foreground: SWI / SNF allows oncogenic transcription. Background: SWI / SNF is the inactivated deactivation of oncogenic transcription. Credit: Ella Maru Studio

Chromatin degradation prevents transcription factors from causing cancer, which may be a potential therapeutic approach for over 90% of prostate cancers.

As researchers have identified several genes responsible for prostate cancer, a new study published in Nature reveals the puppeteer controlling the strings.

The chains: carcinogenic or oncogenic genes, such as the androgen receptor, FOXA1, ERG and MYC.

The Puppeteer: A chromatin remodeling complex called SWI / SNF, which controls how DNA is arranged and compacted to fit in the nucleus of a cell. A key subunit of this complex provides energy to unwrap DNA to provide access to enhancer elements that stimulate the expression of carcinogenic genes.

In the present study, researchers at the University of Michigan Health Rogel Cancer Center demonstrated that the SWI / SNF complex facilitates access to enhancers to which oncogenes can bind and drive downstream gene expression in cancer. Degrading a subunit of this complex blocks oncogenes, like cutting the strings of the puppeteer.

This discovery reveals a new approach to the treatment of prostate cancer fueled by different genetic factors, which together account for more than 90% of all prostate cancers.

In human cells, DNA is wrapped tightly around histone proteins, collectively called chromatin. These form a physical barrier to all DNA-based processes. Specialized protein machines have evolved that consume energy and modulate the physical state of DNA for its functional activation. These complexes work in close collaboration with DNA binding regulatory factors called transcription factors to confer distinct cellular identity and function.

“This is the first demonstration in the field of cancer that blocking access to chromatin can be continued as a route to treat cancer. By compacting the chromatin around these enhancer elements, transcription factors are prevented from binding to enhancer elements that lead to cancer, ”said study author Arul M. Chinnaiyan, MD, Ph.D., director from the Michigan Center for Translational Pathology and SP Hicks. Michigan Medicine Professor of Pathology and Urology.

Researchers looked at several models of prostate cancer that expressed different oncogenes. They found that blocking the SWI / SNF complex slows the growth of cancer cells and induces cell death, especially in tumors induced by FOXA1 or the androgen receptor. There was no effect on benign prostate cells.

In normal development, the SWI / SNF complex is essential. “Normal cells can survive with default levels of gene transcription, but cancer cells are particularly dependent on these enhancer regions. They need access to these activators to increase the expression of oncogenic targets, ”Chinnaiyan said.

Components of the SWI / SNF complex are mutated in a number of cancers, but rarely in prostate cancer. Prostate cancers induced by the androgen receptor or FOXA1 were more sensitive to a SWI / SNF degrader than even cancers in which the subunits were mutated.

“Without having mutations, and with only oncogenic transcription factors involved, prostate cancer cells were extremely sensitive to this degradant, even more so than lung cancer where a component of the pathway was mutated,” Chinnaiyan said. . “By disabling this SWI / SNF complex, we found preferential activity against certain cancers and no toxicity in normal cells or normal tissues. This bodes well for clinical studies using compounds that target this pathway. “

He also suggests the possibility of using this approach for other types of cancer that are dependent on oncogenic transcription factors, including certain multiple myelomas and other blood cancers.

Chinnaiyan Laboratory

The Chinnaiyan laboratory. Credit: Rogel Cancer Center

The researchers used a SWI / SNF degrader under development by the Indian company Aurigene Discovery Technologies. These compounds are under development for future clinical trials.

The Rogel team will continue to study the biology of this complex, help develop compounds that target this complex, and assess what other types of cancer might respond to this approach. For prostate cancer, they are exploring in the laboratory a combination therapy using the SWI / SNF degrader with anti-androgen therapy. This approach is not yet in clinical trials.

Reference: “Targeting SWI / SNF ATPases in Amplifier-Dependent Prostate Cancer” by Lanbo Xiao, Abhijit Parolia, Yuanyuan Qiao, Pushpinder Bawa, Sanjana Eyunni, Rahul Mannan, Sandra E. Carson, Yu Chang, Xiaoju Wang , Yuping Zhang, Josh N Vo, Steven Kregel, Stephanie A. Simko, Andrew D. Delekta, Mustapha Jaber, Heng Zheng, Ingrid J. Apel, Lisa McMurry, Fengyun Su, Rui Wang, Sylvia Zelenka-Wang, Sanjita Sasmal, Leena Khare, Subhendu Mukherjee, Chandrasekhar Abbineni, Kiran Aithal, Mital S. Bhakta, Jay Ghurye, Xuhong Cao, Nora M. Navone, Alexey I. Nesvizhskii, Rohit Mehra, Ulka Vaishampayan, Marco Blanchette, Yuzhuo Wangdarhandar and Santa Sama Sama Aryanul M. Chinnai December 22, 2021, Nature.
DOI: 10.1038 / s41586-021-04246-z

Additional authors: Lanbo Xiao, Abhijit Parolia, Yuanyuan Qiao, Pushpinder Bawa, Sanjana Eyunni, Rahul Mannan, Sandra E. Carson, Yu Chang, Xiaoju Wang, Yuping Zhang, Josh N. Vo, Steven Kregel, Stephanie A. Simko, Andrew D Delekta, Mustapha Jaber, Heng Zheng, Ingrid J. Apel, Lisa McMurry, Fengyun Su, Rui Wang, Sylvia Zelenka-Wang, Sanjita Sasmal, Leena Khare, Subhendu Mukherjee, Chandrasekhar Abbineni, Kiran Aithal, Mital S. Bhakta, Jay Ghurye, Xuhong Cao, Nora M. Navone, Alexey I. Nesvizhskii, Rohit Mehra, Ulka Vaishampayan, Marco Blanchette, Yuzhuo Wang, Susanta Samajdar, Murali Ramachandra

Funding: Prostate Cancer Foundation Challenge Award, National Cancer Institute Grants P50-CA186786, R35-CA231996, U01-CA214170, P30-CA046592, Department of Defense Prostate Cancer Research Program W81XWH-21-1-0500 . Chinnaiyan is a Howard Hughes Medical Institute Fellow, A. Alfred Taubman Fellow, and Professor at the American Cancer Society.

Disclosure: S. Sasmal., LK, SM, CA, S. Samajdar, KA and MR are affiliated with Aurigene Discovery Technologies. JG, MSB and MB are affiliated with Dovetail Genomics. AMC is a co-founder and sits on the scientific advisory boards of LynxDx, Oncopia and Esanik. AMC sits on the Scientific Advisory Board of Tempus and Ascentage.


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Bathinda: Cancer patients forced into private facilities: The Tribune India https://parentraide-cancer.org/bathinda-cancer-patients-forced-into-private-facilities-the-tribune-india/ Mon, 27 Dec 2021 03:44:00 +0000 https://parentraide-cancer.org/bathinda-cancer-patients-forced-into-private-facilities-the-tribune-india/ Bathinda, December 26 The treatment of cancer patients is negatively affected as nurses, technical staff and service attendants at the Advanced Cancer Institute-cum-Hospital have been restless for a week. Hospital authorities, who were already grappling with a staff shortage, are now finding it very difficult to provide care. Do our best The work is affected […]]]>

Bathinda, December 26

The treatment of cancer patients is negatively affected as nurses, technical staff and service attendants at the Advanced Cancer Institute-cum-Hospital have been restless for a week.

Hospital authorities, who were already grappling with a staff shortage, are now finding it very difficult to provide care.

Do our best

The work is affected due to the ongoing employee strike. We do our best to keep patients in pain. – Deepak Arora, Director, Cancer Hospital

Cancer patients admitted to the ward ward (IPD) were discharged and new patients were only seen in the ambulatory care ward (OPD).

As the quality of treatment was also compromised, critical patients were forced to go to private hospitals, costing them exorbitantly. Most of the patients who visit the hospital come from the lower strata of society who cannot afford expensive treatment.

The cancer institute not only welcomes patients from Bathinda or other districts of Malwa, but also residents of neighboring districts of Haryana and Rajasthan.

Due to the ongoing protest, there are no staff to work the night shift and the operation of the medical laboratory has also been affected.

An employee on condition of anonymity said: “It’s the patients who ultimately suffer. Staff have the right to protest, but they must devote time to the well-being of cancer patients.

Dr Deepak Arora, Director of the Advanced Cancer Institute-cum-Hospital, said: “The patients are examined and chemotherapy sessions take place. Some units of the hospital are not operational. – TNS


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