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Fight ras “without problem” genes

Patients with pancreatic cancer have a bad overall prognosis: in most patients, the disease has already spread at the time of diagnosis, which causes limited treatment options. Almost 90% of pancreatic cancers are driven by Kras Mutations, the mutation of the most frequented cancer gene through types of cancer, which researchers have long considered “without problem”. In 2021, the first Kras The inhibitor has been approved to treat lung cancer not with small cells with Kras G12C changes, but with longer follow -up, it has become clear that Kras-The mutant cancers can quickly evolve to withstand targeted therapies to a specific form of the gene mutation.

“We were excited by the prospect of Ras The inhibition of pancreatic cancer, which remains one of the deadliest and most difficult to treat cancer, “said Ben Stanger, PHD, Professor Hanna Wise in cancer and director of the Penn Pannatic Cancer Research Center. Kras The inhibitors had a limited impact on cancer care, this research shows that Ras Inhibition tools can have a stimulating immune effect, which makes them ideal to associate with immunotherapy for a longer and better treatment response. “”

Previous research carried out by Stanger and Robert Vonderheide, MD, DPHil, director of the Abramson Cancer Center, who co-correside author of this study, has shown that a small molecule inhibitor specifically specifically targeting targeting specifically Kras G12D, The form of the mutation more commonly found in pancreatic cancer, stimulated the immune system while shrinking tumors or stopping cancer growth in preclinical pancreatic cancer models.

A new type of inhibitor

In this study, researchers used Multi-Sélective RAS (ON) inhibitors, the Daraxonrasib Investigation Agent (RMC-6236) and the preclinical tool composed RMC-7977 (both discovered by Revolution Medicines, whose scientists contributed to the study). These inhibitors use a different action mechanism from that of most Kras inhibitors (including that of the previous study) to target the activity or state of several forms of Ras Mutations.

“The advantage of this” multi-selective “approach is that inhibitors are designed to inhibit multiple Ras mutations, therefore if cancer lumps and another type of Ras The mutation emerges, the treatment cannot necessarily stop working, “said Vonderheide.

The research team noted that not only was the multi-selective inhibition of AR (ON) was effective in preclinical pancreatic cancer models, but it was even more effective when combined with immunotherapy. Using the combined approach, all mouse models had a narrowing of the tumor and half had a complete response, which means that the tumor was eliminated.

The research team used an immunocompetent model developed in Penn considered to be the gold stallion around the world to assess potential therapies for pancreatic canal adenocarcinoma. This model allows the tumor to evolve spontaneously after implantation, which makes it possible to discern the impact of the drug on the surrounding tumor microenvironment. The research team revealed that multi-selective inhibition of RAS (ON) reshaped tumor microenvironnement by bringing more T cells and other immune cells, which makes the tumor particularly receptive to immunotherapy.

Following steps and information on clinical trials

Daraxonrasib (RMC-6236) is already tested in clinical trials in the United States. A clinical trial testing RAS inhibitors (ON) with other anti-cancer agents in certain patients with solid gastrointestinal tumors is now open to several sites across the country, including in Penn Medicine. Click here for more information on the study.

“We hope we are starting to break the code on immunotherapy and Ras Therapy for pancreatic cancer, “said Vonderheide.” After decades of limited progress, it is encouraging to see new processing approaches to the clinic for patients. “”

The study was supported by Revolution Medicines, The National Institutes of Health (R01CA2522225, R01CA276512, P30DK050306, P30CA016520) The Ministry of Defense (W81XWH2210730), molecular pathology and Core of Love for Life, Basser Center for Brca, and Pandre.

Information for patients interested in joining a clinical trial: Visit the Information Service on clinical trials of Abramson Cancer Center of Penn Medicine online or call 1-855-216-0098 to speak to a clinical trial browser.

Publisher’s note: Vonderheide is an inventor on patents relating to cancer cell immunotherapy and Kras immune epitopes.

Fight ras “without problem” genes

Patients with pancreatic cancer have a bad overall prognosis: in most patients, the disease has already spread at the time of diagnosis, which causes limited treatment options. Almost 90% of pancreatic cancers are driven by Kras Mutations, the mutation of the most frequented cancer gene through types of cancer, which researchers have long considered “without problem”. In 2021, the first Kras The inhibitor has been approved to treat lung cancer not with small cells with Kras G12C changes, but with longer follow -up, it has become clear that Kras-The mutant cancers can quickly evolve to withstand targeted therapies to a specific form of the gene mutation.

“We were excited by the prospect of Ras The inhibition of pancreatic cancer, which remains one of the deadliest and most difficult to treat cancer, “said Ben Stanger, PHD, Professor Hanna Wise in cancer and director of the Penn Pannatic Cancer Research Center. Kras The inhibitors had a limited impact on cancer care, this research shows that Ras Inhibition tools can have a stimulating immune effect, which makes them ideal to associate with immunotherapy for a longer and better treatment response. “”

Previous research carried out by Stanger and Robert Vonderheide, MD, DPHil, director of the Abramson Cancer Center, who co-correside author of this study, has shown that a small molecule inhibitor specifically specifically targeting targeting specifically Kras G12D, The form of the mutation more commonly found in pancreatic cancer, stimulated the immune system while shrinking tumors or stopping cancer growth in preclinical pancreatic cancer models.

A new type of inhibitor

In this study, researchers used Multi-Sélective RAS (ON) inhibitors, the Daraxonrasib Investigation Agent (RMC-6236) and the preclinical tool composed RMC-7977 (both discovered by Revolution Medicines, whose scientists contributed to the study). These inhibitors use a different action mechanism from that of most Kras inhibitors (including that of the previous study) to target the activity or state of several forms of Ras Mutations.

“The advantage of this” multi-selective “approach is that inhibitors are designed to inhibit multiple Ras mutations, therefore if cancer lumps and another type of Ras The mutation emerges, the treatment cannot necessarily stop working, “said Vonderheide.

The research team noted that not only was the multi-selective inhibition of AR (ON) was effective in preclinical pancreatic cancer models, but it was even more effective when combined with immunotherapy. Using the combined approach, all mouse models had a narrowing of the tumor and half had a complete response, which means that the tumor was eliminated.

The research team used an immunocompetent model developed in Penn considered to be the gold stallion around the world to assess potential therapies for pancreatic canal adenocarcinoma. This model allows the tumor to evolve spontaneously after implantation, which makes it possible to discern the impact of the drug on the surrounding tumor microenvironment. The research team revealed that multi-selective inhibition of RAS (ON) reshaped tumor microenvironnement by bringing more T cells and other immune cells, which makes the tumor particularly receptive to immunotherapy.

Following steps and information on clinical trials

Daraxonrasib (RMC-6236) is already tested in clinical trials in the United States. A clinical trial testing RAS inhibitors (ON) with other anti-cancer agents in certain patients with solid gastrointestinal tumors is now open to several sites across the country, including in Penn Medicine. Click here for more information on the study.

“We hope we are starting to break the code on immunotherapy and Ras Therapy for pancreatic cancer, “said Vonderheide.” After decades of limited progress, it is encouraging to see new processing approaches to the clinic for patients. “”

The study was supported by Revolution Medicines, The National Institutes of Health (R01CA2522225, R01CA276512, P30DK050306, P30CA016520) The Ministry of Defense (W81XWH2210730), molecular pathology and Core of Love for Life, Basser Center for Brca, and Pandre.

Information for patients interested in joining a clinical trial: Visit the Information Service on clinical trials of Abramson Cancer Center of Penn Medicine online or call 1-855-216-0098 to speak to a clinical trial browser.

Publisher’s note: Vonderheide is an inventor on patents relating to cancer cell immunotherapy and Kras immune epitopes.

Fight ras “without problem” genes

Patients with pancreatic cancer have a bad overall prognosis: in most patients, the disease has already spread at the time of diagnosis, which causes limited treatment options. Almost 90% of pancreatic cancers are driven by Kras Mutations, the mutation of the most frequented cancer gene through types of cancer, which researchers have long considered “without problem”. In 2021, the first Kras The inhibitor has been approved to treat lung cancer not with small cells with Kras G12C changes, but with longer follow -up, it has become clear that Kras-The mutant cancers can quickly evolve to withstand targeted therapies to a specific form of the gene mutation.

“We were excited by the prospect of Ras The inhibition of pancreatic cancer, which remains one of the deadliest and most difficult to treat cancer, “said Ben Stanger, PHD, Professor Hanna Wise in cancer and director of the Penn Pannatic Cancer Research Center. Kras The inhibitors had a limited impact on cancer care, this research shows that Ras Inhibition tools can have a stimulating immune effect, which makes them ideal to associate with immunotherapy for a longer and better treatment response. “”

Previous research carried out by Stanger and Robert Vonderheide, MD, DPHil, director of the Abramson Cancer Center, who co-correside author of this study, has shown that a small molecule inhibitor specifically specifically targeting targeting specifically Kras G12D, The form of the mutation more commonly found in pancreatic cancer, stimulated the immune system while shrinking tumors or stopping cancer growth in preclinical pancreatic cancer models.

A new type of inhibitor

In this study, researchers used Multi-Sélective RAS (ON) inhibitors, the Daraxonrasib Investigation Agent (RMC-6236) and the preclinical tool composed RMC-7977 (both discovered by Revolution Medicines, whose scientists contributed to the study). These inhibitors use a different action mechanism from that of most Kras inhibitors (including that of the previous study) to target the activity or state of several forms of Ras Mutations.

“The advantage of this” multi-selective “approach is that inhibitors are designed to inhibit multiple Ras mutations, therefore if cancer lumps and another type of Ras The mutation emerges, the treatment cannot necessarily stop working, “said Vonderheide.

The research team noted that not only was the multi-selective inhibition of AR (ON) was effective in preclinical pancreatic cancer models, but it was even more effective when combined with immunotherapy. Using the combined approach, all mouse models had a narrowing of the tumor and half had a complete response, which means that the tumor was eliminated.

The research team used an immunocompetent model developed in Penn considered to be the gold stallion around the world to assess potential therapies for pancreatic canal adenocarcinoma. This model allows the tumor to evolve spontaneously after implantation, which makes it possible to discern the impact of the drug on the surrounding tumor microenvironment. The research team revealed that multi-selective inhibition of RAS (ON) reshaped tumor microenvironnement by bringing more T cells and other immune cells, which makes the tumor particularly receptive to immunotherapy.

Following steps and information on clinical trials

Daraxonrasib (RMC-6236) is already tested in clinical trials in the United States. A clinical trial testing RAS inhibitors (ON) with other anti-cancer agents in certain patients with solid gastrointestinal tumors is now open to several sites across the country, including in Penn Medicine. Click here for more information on the study.

“We hope we are starting to break the code on immunotherapy and Ras Therapy for pancreatic cancer, “said Vonderheide.” After decades of limited progress, it is encouraging to see new processing approaches to the clinic for patients. “”

The study was supported by Revolution Medicines, The National Institutes of Health (R01CA2522225, R01CA276512, P30DK050306, P30CA016520) The Ministry of Defense (W81XWH2210730), molecular pathology and Core of Love for Life, Basser Center for Brca, and Pandre.

Information for patients interested in joining a clinical trial: Visit the Information Service on clinical trials of Abramson Cancer Center of Penn Medicine online or call 1-855-216-0098 to speak to a clinical trial browser.

Publisher’s note: Vonderheide is an inventor on patents relating to cancer cell immunotherapy and Kras immune epitopes.