Pancreatic cancer is one of the most lethal malignancies with few treatment options. Its five-year survival rate is only about 10% in the US. Several treatment options are available for pancreatic cancers, including surgery, chemotherapy, radiation therapy, immunotherapy, and combinational therapies. However, these therapies are ineffective for most patients, and the outcomes are far from satisfactory. Current Immunotherapy Has Limited Effects on Pancreatic Cancer Immunotherapies hold great potential for several types of cancer, but they have limitations to pancreatic cancer. Antibody-based immunotherapy, such as the checkpoint inhibitor drug pembrolizumab, only works for a small portion (1-2%) of pancreatic patients who carry the genomic abnormalities called “mismatch repair-deficient (dMMR) or “microsatellite instability stability high” (MSI-H). T-cell-based immunotherapy, such as Chimeric Antigen Receptor (CAR) T-cell therapy or CAR-T therapy, has shown limited treatment effects on pancreatic cancer because it is difficult for T-cells to penetrate the tumors and kill them. Pancreatic Cancers are Often Called “Cold Tumors” Pancreatic cancers are “cold tumors” or “immune-excluded tumors” because the cancer-killing T-cells couldn’t efficiently infiltrate the tumor and only stay at the margins. Research data shows that pancreatic ductal adenocarcinoma (PDAC) builds up a surrounding microenvironment that suppresses the cancer-killing functions of the immune system. To turn the “cold tumor” into a “hot tumor,” researchers must explore novel approaches to disrupt the tumor-friendly microenvironment around the pancreatic tumors and enable more tumor-killing T-cells to infiltrate the tumor sites.  Novel CAR-T Cells May Infiltrate Pancreatic Cancer More Efficiently Avery D. Posey, Jr., Ph.D. at the Center for Cellular Immunotherapy, University of Pennsylvania School of Medicine, is leading a research team to develop a novel type of CAR-T Cell therapy to overcome the limitation of current cell therapy procedures. Unlike antibody drugs, CAR-T therapy uses living cells to treat cancer in three steps. First, doctors collect the cancer-fighting T-cells from patients. Then, specialized technicians will modify those cells in the laboratory with genetic engineering technology. The engineered T-cells will be tailored to attack the patient’s tumor specifically. They are also armed with new genes, enabling them to penetrate tumors more efficiently than the patient’s natural T-cells. As the final step, modified CAR T-cells will be infused back into the patient to let them find and kill the cancer cells. How We Make An Impact With the NFCR’s support, Dr. Posey is collaborating with Dr. Courtney Houchen at the University of Oklahoma Health Sciences Center to conduct the research. They will make the novel CAR-T cells ready for human clinical trials after generating enough data in their laboratories.  Learn more about Dr. Posey’s research project on the novel CAR-T Therapy by watching this video. References: CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers. National Cancer Institute, March 10, 2022.

Did you know that normal oxygen levels inside and surrounding the tumors are critical for effective cancer treatment? Studies have found that when a tumor stays in a low oxygen status called hypoxia, it becomes resistant to many treatments. These treatments include radiation, chemotherapy, targeted therapy, and immunotherapy. The hypoxia also promotes tumor progression, a dangerous condition for cancer patients.  Two Approaches to Reverse the Hypoxia Condition in Tumors  Through continued research partially funded by the National Foundation for Cancer Research (NFCR), scientists have revealed the leading cause of hypoxia. Hypoxia happens because of the formation of defective blood vessels in tumor tissues. To repair the defected blood vessels and reverse the hypoxia condition, a research team led by NFCR-funded scientist Dr. Rakesh K. Jain, Director of the Steele Laboratories for Tumor Biology at Massachusetts General Hospital, has developed two approaches. The first one is to inhibit a cellular signaling system called Vascular Endothelial Growth Factor (VEGF) Pathway in tumor cells. This method could transiently improve blood flow and oxygenation in tumors. The other approach utilizes angiotensin receptor blockers, such as the high blood pressure drug Losartan to alleviate the blood vessel collapse caused by growing tumor mass. Reduced Hypoxia Could Improve Certain Cancer’s Survival Rate  Research data shows that both approaches hold the promise to reduce tumor hypoxia by improving oxygenation in tumors. Additionally, these methods increase blood flow, improving the delivery of anticancer drugs or cancer-killing immune cells to the tumor sites. A clinical trial also showed that the combination of Losartan with radiation and chemotherapy significantly improved survival rates for pancreatic cancer. Understanding the Dynamics of Hypoxia is Critical for Treatment However, Dr. Jain's team found that the two approaches don't always produce the same effects on patients with different diseases. Through further research, Dr. Jain's team revealed that the tumor hypoxia doesn't stay at one level all the time. The hypoxia levels vary in different tumor locations and times. As such, the hypoxia-reversion approaches won't achieve their potential therapeutic effects without a clear understanding of the spatial and temporal heterogeneity of tumor hypoxia.  Research Innovation Will Improve Patients’ Treatment Outcomes Constant innovation is always the main driving force in research. To measure the temporal and spatial changes in oxygen in tumors, Dr. Jain's team developed a unique microscopy system and a special low-molecular-weight agent called palladium porphyrin probe. This research system enables the researchers to understand the dynamic changes in oxygen level and hypoxia condition after applying Losartan and VEGF pathway inhibitors.  Dr. Jain's research results were published in the journal of Clinical Cancer Research on May 18, 2022. More data will be collected and analyzed while the project continues. Future data will provide insightful information to help doctors optimize the dose and schedule of Losartan and other medications. With improved oxygenation and reduced hypoxia condition in tumors, patients will have lower rates of drug resistance and improved therapeutic outcomes in the future. References: Multiphoton phosphorescence quenching microscopy reveals kinetics of tumor oxygenation during anti-angiogenesis and angiotensin signaling inhibition. Clinical Cancer Research, May 18, 2022. Novel protocol improves pancreatic cancer outcomes. The Harvard Gazette, May 30, [...]

NFCR Chief Medical Officer Shares His Expertise for Improved Pancreatic Cancer Awareness The National Foundation for Cancer Research (NFCR)’s Dr. Brian Leyland-Jones contributed to the popular online platform Eat This, Not That!’s feature in efforts to spread awareness of one of the most deadly and difficult to detect cancers: 11 Warning Signs of Pancreatic Cancer. Dr. Leyland-Jones’ career spans decades, and has led him to become an authority within the pancreatic cancer-fighting community. Dr. Leyland Jones serves as Board Member and Chief Medical Officer for NFCR, offering his extensive expertise to NFCR’s fundraising missions. Boasting over 100 million readers, Eat This, Not That! publishes expert- and research-backed tips on food, nutrition, and health. Dr. Leyland-Jones’ tips on pancreatic cancer awareness help strengthen the deep catalogue of recipes, diet recommendations, and general wellness tips on the popular online platform. Warning Signs Early detection is crucial for early intervention with pancreatic cancer. The disease has an overall five-year survival rate of just 9% and is likely to rise to become the second leading cause of cancer-related deaths in the U.S. by the year 2030. These facts, coupled with pancreatic cancer’s significant reputation as one of the silent killers, showcase the importance of knowing these 11 warning signs: Blood Clots Ascites Jaundice Sudden Weight Loss Upper Abdominal Pain Depression and Anxiety (Before Diagnosis) Nausea and Vomiting Diabetes Pale Feces and Dark Urine Enlarged Gallbladder or Liver Unexplainable Fatigue Outside of these symptoms, Dr. Leyland-Jones emphasizes the importance of keeping up-to-date on your yearly physicals, stating, “It is very difficult to detect early. For yearly physicals, some people also get PET scans and CT scans. However, the progression is so fast, these kinds of scans would need to be done every six months.” With approximately 60,000 new cases per year, pancreatic cancer will continue to be a significant concern. Know these warning signs and keep up with day-to-day wellness and yearly physicals in order to stay on top of your health!   Did you know that November is Pancreatic Cancer Awareness Month? Subscribe to NFCR social media channels to stay up to date on the latest developments in the fight against pancreatic cancer. You can also visit our donation page to join in our fundraising efforts! Additional Reads You May Enjoy: Thunder God Vine: A Powerful Discovery for Pancreatic Cancer Patients 5 Tips for Eating Healthy While Traveling Coping With Cancer—It’s Different for Everyone Receive our monthly e-newsletter and blogs featuring stories of inspiration, support resources, cancer prevention tips and more. Sign up here.