Pancreatic Cancer Treatment: Options, Testing, and What to Ask

•The overall five-year survival rate is 7.2%.

•Looking only at pancreatic cancers that have not spread beyond the pancreas (“localized” cancers), the survival rate is 27.1%.

•For cancers that have spread, but only to nearby areas (“regional” cancers), the survival rate is 10.7%.

•Metastatic (Stage IV) pancreatic cancer has a five-year survival rate of 1 percent. If they then search for standard treatment options, they find:

•Pancreatic cancer treatment may involve surgery, chemotherapy, radiation therapy, vaccination, pain management, immunotherapy and dietary changes.

•Surgery remains the gold standard of treatment, but can be achieved only in a small number of patients whose cancer is caught early and is localized. The main surgical approach (the "Whipple" procedure) involves removing the head (wide part) of the pancreas, which is connected to the top part of the small intestine. Those who undergo a successful Whipple procedure may boost their 5-year survival rate up to 25%.

•Pancreatic cancer which has spread more is treated with chemotherapy and possibly radiation. Despite the grim survival statistics and poor prognosis associated with this disease, improvements in supportive care, chemotherapy, and molecular diagnostics are enabling some patients to live longer and better. Key among these developments are drugs which target a mutation (e.g., KRAS). If you have this mutation, you have a new treatment option to consider. John Strickler, MD, Associate Professor of Medicine in the Division of Medical Oncology at Duke University and co-leader of the Molecular Tumor Board and Precision Cancer Medicine and Investigational Therapeutics Research Program, is uniquely qualified to discuss advances in pancreatic cancer care. Dr. Strickler specializes in the treatment of esophageal, gastric, pancreatic, and colorectal cancers. with a focus on clinical trials. Clinical trial patie creatic Cancer” and Investigational Therapeutics Research Program, is uniquely qualified to discuss advances in pancreatic cancer care. Dr. Strickler specializes in the treatment of esophageal, gastric, pancreatic, and colorectal cancers. with a focus on clinical trials. Clinical trial patients usually come to him looking for an alternative therapy once standard treatments have not been effective. He recently published results on a study of pancreatic cancer patients with a specific mutation (KRAS G12C). What are the improvements in treatments for pancreatic cancer coming online today?

•Personalized medicine is emerging as a key approach for pancreatic cancer, with targeted therapies based on your tumor profile showing promising results. For example, drugs targeting KRAS and BRCA mutations are showing promise in clinical trials and entering the standard treatment guidelines.

•Genetic testing and molecular profiling are becoming increasingly important to identify if you can benefit from targeted therapies.

•Early detection remains crucial for improving patient outcomes. “Germline” (hereditary) testing, a type of genetic (DNA) testing that looks for inherited mutations or inherited predispositions to certain types of cancers via cheek swab, spit sample or a blood draw, can help identify individuals at higher risk. What are future improvements to keep an eye on?

•Testing advances : New tests, such as RNA sequencing and proteomics, will provide a richer profile of your tumor and tumor microenvironment.

•Liquid biopsies (blood draws) hold promise for easier cancer diagnosis and treatment monitoring, although challenges remain in their accuracy for pancreatic cancer. If you can pick up pancreatic cancer earlier, say five years before it becomes a full blown cancer, you might be protected from an aggressive malignancy.

•Cancer vaccines: Early data from studies indicate that cancer vaccines may generate an anti-tumor immune response, with hints of beneficial impacts in early pilot studies.

•Cryotherapy: Cryotherapy (sometimes known as cold therapy, the local or general use of low temperatures for treatment) is b eing explored as a potential treatment, with some case studies showing positive results.

•Radioligands: Radioligands (a kind of radiation therapy made of a radioisotope and a molecule that binds to specific markers on cancer cells) have potential for pancreatic cancer treatment, particularly for neuroendocrine tumors (cancer in the nerves or glands that produce hormones).

•Drug repurposing : We will develop better ways to fund research on therapies that don't have much of a financial incentive – that don't cost $50,000 per dose, but cost $5 a dose. What are the challenges in finding additional future treatments for pancreatic cancer? Challenges remain in developing effective treatments for pancreatic cancer due to factors like resistance and tumor complexity. New strategies are needed to overcome these hurdles. For example:

•Heterogeneity of resistance : Pancreatic cancer cells will typically develop multiple resistance mutations simultaneously. For example, if you have cancer in five spots in your body, each spot may develop an independent and unrelated resistance mutation. Even if you could target one of them, it would leave the other four spots untreated.

•Finding a treatment for a target : 90% of pancreas cancers have a KRAS mutation. If you were to choose one mutation to target in pancreas cancer, this would be it. The problem is that it has taken us literally decades to figure out how to target this mutation.

•Adverse selection for trials : The field for cancer vaccine trials has been held back because these trials tend to be conducted in patients who have more advanced disease. It may be that vaccine trials are at their best when the patient has minimal disease. And because patients may have just had surgery, it would take sometimes years to even show that you've altered outcomes for them, compared to a control.

•Merging diagnostics with bioinformatics : We will need bioinformatics and machine learning and AI to take the information from advanced tests (like RNA sequencing and proteomics) and apply it to understand the disease and guide therapies. We're going to need a whole next generation of therapies that are designed to target those proteomic signals.

•Finding signal in the blood : Pancreatic tumors have very little active tumor content, so they don't produce a lot of circulating tumor DNA into the bloodstream that can be captured on a blood test.

•Test accuracy: When you are trying to get an early warning for a cancer that is aggressive and doesn’t happen very often, you need a test with very high specificity (low false positives) and sensitivity (low false negatives) to avoid the expense and upset of incorrectly telling someone whether they have the disease or not.

•Treatment proliferation : It is difficult for an oncologist who is treating many kinds of cancers to keep up with the evolving treatment landscape. Patients should be empowered to know their own disease. What can you do?

•Get genetic testing: You should ask your doctor, “Have you done the molecular profiling on my cancer? Can I see the report?” You should have the report printed out and bring it with you when you get a consultation because that's something that typically exists outside the medical chart.

•Learn: Keep up with the evolving pancreatic cancer testing and treatment landscape.

•Engage: Get involved in patient advocacy groups and funding pancreati c cancer research. The information and opinio opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Meeting Notes KEYWORDS pancreas cancer, KRAS, therapies, mutation, patients, cancer, tumor, pancreatic cancer, target, prostate cancer, drugs, vaccine, test, BRCA, work, call, people, germline, disease, chemotherapy SPEAKERS John Strickler (66%), Roger Royse (8%), Allen Morris (8%), Rick Davis (8%), Richard Anders (4%), Debbie Denison (2%), Brad Power (2%), Brian McCloskey (1%), Jeff Krolick (1%) OUTLINE 1.Recent advances in pancreatic cancer treatment. (0:06) 2.Personalized cancer medicine for pancreas cancer. (1:31) 3.Targeting KRAS mutations in pancreatic cancer. (6:47) 4.Pancreatic cancer treatment and new approaches. (12:36) 5.Using cryotherapy for cancer treatment. (17:50) 6.Liquid biopsies for pancreatic cancer diagnosis and treatment. (27:01) 7.Pancreatic cancer treatment and genetic mutations. (33:49) 8.Early detection of pancreatic cancer through blood tests. (38:25) 9.Radioligands for pancreatic cancer treatment. (43:29) 10.Cancer treatment resistance and empowering patients. (50:12) 11.KRAS mutations and resistance in cancer treatment. (53:56) SUMMARY Recent advances in pancreatic cancer treatment.

•Dr. John Strickler discusses recent advances in pancreatic cancer treatment at Duke University. Personalized cancer medicine for pancreas cancer.

•John Strickler discusses the future of pancreas cancer treatment, highlighting the importance of personalized cancer medicine.

•He believes that personalized medicine has the potential to improve outcomes for pancreas cancer patients, minimizing toxicity and maximizing effectiveness.

•In 2013, there were no targeted therapies for pancreas cancer, but now there are FDA- approved therapies for germline BRCA mutations.

•Profiling tumors for driver mutations can improve survival, with survival doubling when treated with targeted therapy. Targeting KRAS mutations in pancreatic cancer.

•KRAS mutations are a main driver of pancreas cancer, responsible for 87% of cases.

•John Strickler highlights promising breakthroughs in targeting KRAS mutations in pancreatic cancer, with minimal side effects

•New drugs targeting KRAS mutations show promise in clinical trials, including high potency targeting, degraders, molecular glues, and covalent bonds. Pancreatic cancer treatment and new approaches.

•John Strickler emphasizes the importance of genetic testing and molecular profiling for pancreas cancer patients, as it can help identify potential eligibility for targeted therapies and improve treatment outcomes.

•He notes that cancer vaccines are a promising area of research.

•He mentions early data indicating that cancer vaccines may generate an anti-tumor immune response, with hints of beneficial impacts for patients in early pilot studies.

•Roger Royse, a pancreatic cancer patient, is participating in a cancer vaccine trial with no side effects after 6 doses, but with no visible changes on scans yet. Using cryotherapy for cancer treatment.

•Allen Morris questions the conventional wisdom that cold tumors are the least likely to respond to therapeutic vaccines, citing promising signals in other tumor types, including pancreatic cancer.

•Dr. Gary Onik uses cryotherapy to produce an auto vaccination for prostate cancer, with a cure rate of no evidence of disease times five years, despite being a stage four metastatic cancer.

•Allen Morris shares a case of a patient with liver metastases who had a complete response to cryotherapy, which is rare in the field of oncology.

•Roger Royse agrees that case reports like this can inspire research and funding, but emphasizes the need for hypothesis-driven studies to make progress in the field.

•John Strickler discusses the need for new therapies to treat pancreas cancer, citing poor long-term outcomes with standard of care.

•John Strickler and Roger Royse discuss the potential of proteomics to guide therapy, with John Strickler suggesting it may become part of standard of care in the future, but this is years away.. Liquid biopsies for pancreatic cancer diagnosis and treatment.

•Brad Power discusses the potential of liquid biopsies for cancer diagnosis and monitoring, including the advantages of using RNA over DNA.

•John Strickler highlights the limitations of blood-based profiling for pancreas cancer, including the difficulty in detecting active tumor content in desmoplastic lesions.

•He highlights the limitations of blood tests for pancreas cancer detection, but sees potential in their use for early detection and preventive medicine.

•Jeff Krolick discusses challenges in funding research on off-label drug uses for pancreatic and prostate cancer, citing high costs and lack of financial incentives. Pancreatic cancer treatment and genetic mutations.

•Rick Davis asks about BRCA mutations in prost prostate cancer and their monitoring for pancreatic cancer.

•Olaparib FDA-approved for germline BRCA-mutated pancreas cancer, but controversial due to lack of survival benefit. Early detection of pancreatic cancer through blood tests.

•John Strickler discusses the potential benefits of germline testing for pancreatic cancer patients.

•Roger Royse shares his story of early detection and successful treatment of pancreatic cancer, highlighting the importance of early detection for improving outcomes.

•John Strickler expresses concerns about the specificity of early detection assays, acknowledging the need for high sensitivity and specificity to avoid false positives and unnecessary follow-up tests. Radioligands for pancreatic cancer treatment.

•Radioligands have potential for pancreatic cancer treatment, despite limited development in this area.

•Brian McCloskey discusses use of radioligands for pancreatic neuroendocrine cancer treatment, with a focus on leutetium and new developments in DLL3.

•John Strickler suggests targeted therapies may be more effective for CML than solid tumors due to fewer mutations. Cancer treatment resistance and empowering patients.

•John Strickler discusses challenges in treating solid tumors with targeted therapies, including lung cancer, and the need to develop new strategies to prevent resistance.

•Oncologists face challenges keeping up with the rapidly evolving treatment landscape for rare cancers. KRAS mutations and resistance in cancer treatment.

•John Strickler discusses challenges in developing drugs for KRAS mutations, including the need to attack a "light switch" when it's in the "on" position.

•He highlights Revolution Medicine's pipeline of drugs designed to target KRAS variants, showing promising data in pancreatic cancer.

•John Strickler explains that pancreatic cancer cells typically develop multiple simultaneous mutations to resist treatment, making it challenging to target a single mutation.

•Dr. Strickler explains the complexity of targeting KRAS mutations in cancer, which can be in an "on" or "off" state, and how new drugs are being developed to target it in both states. Meeting