Cancer Diagnosis

NFCR-supported researchers Dr. Suzanne Topalian of Johns Hopkins University and her collaborator Dr. Paul Nghiem of the University of Washington co-authored a study titled "A minimal gene set characterizes TIL specific for diverse tumor antigens across different cancer types" that was published in Nature Communications. The study identified a small group of key genes that help find special immune cells called tumor-infiltrating lymphocytes (TILs) that naturally fight cancer.  These immune cells can recognize and attack different types of tumors, making them important for cancer treatment. Understanding which genes control these cells could help researchers develop better cancer therapies, especially immunotherapy, which boosts the body’s natural defenses against cancer.  This discovery may lead to more effective ways to identify and activate the immune system to fight cancer. From Dr. Suzanne Topalian: Our continuing studies to profile T cells recognizing virus-positive vs virus-negative MCCs will build on these initial findings to provide an in-depth characterization of the immune response against MCCs.  We anticipate that such work may lead to enhanced therapeutics and immune monitoring tools. Please know how much NFCR funding is appreciated in support of these investigations. Your support is making a difference in the fight against cancer! Donate today and be a part of the cure with NFCR. About Immunotherapy Cancer Immunotherapy is a groundbreaking new frontier in cancer treatment that helps empower patients’ own immune systems to recognize and attack cancer cells, providing new hope and critical treatment options for many patients with advanced cancers that were previously difficult to treat effectively. Learn More>>> Collaboration to Accelerate Discoveries With NFCR support, Dr. Nghiem and Dr. Topalian are collaborating to tackle the problem of why and how the body’s immune system sees virus-induced and UV light-induced MCC differently. Their studies of immune responses will help determine new combination therapies to save more patients from MCC. About Suzanne Topalian Dr. Suzanne Topalian is a physician-scientist whose studies of anti-tumor immunity have been foundational in developing cancer immunotherapy. Her research catalyzed the cancer community to develop the current FDA approval of 6 different checkpoint inhibitors (ICIs) for 17 types of cancer. About Paul Nghiem Dr. Paul Nghiem is a physician-scientist and leader in the research and treatment of Merkel cell carcinoma (MCC), a rare and deadly skin cancer. Studies by Dr. Nghiem’s team have resulted in the first two FDA-approved therapies for MCC. Sign-up to Stay Informed About Cancer Research Breakthroughs with NFCR!

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.

Immunotherapy has changed the landscape of cancer medicine. The good news about its recent success in treating rectal cancer marked a new milestone in curing cancers. Rectal Cancers Are Gone After the Treatment A research paper published in the New England Journal of Medicine on June 23, 2022, reported that 12 patients with rectal cancer treated with the immunotherapy drug dostarlimab have all achieved complete remission – the cancers vanished or are undetectable after the treatment.  Doctors followed up with these 12 patients for 6 to 25 months after the treatment, and the results from all patients are remarkable:  The tumor is undetectable on MRI scan and endoscopic examination; No progression or recurrence had been reported during the follow-up period; No severe adverse events have been reported for all patients since the treatment. This type of outstanding treatment outcome has not happened before. Genetic Testing Played a Critical Role  This unprecedented treatment outcome proved that developing genetic testing technology and applying it to cancer treatment is worth its decade-long research efforts.  All patients received genetic testing before being selected for the clinical trial. These 12 patients were recruited for the trial because they tested positive for a genetic instability called mismatch repair deficiency (MMR-d). Research has shown that patients with MMR-d may respond better to dostarlimab treatment than patients without it. The genetic testing on MMR-d played a critical role in successfully treating this cohort of patients. Actually, the combination of genetic-testing-based patient selection and immunotherapy led to the complete remission of all patients in this clinical trial.  NFCR is a Pioneer in Genetic Testing Research The National Foundation for Cancer Research (NFCR) is a pioneer in funding genetic testing research. As early as 2005, NFCR started to support cancer molecular profiling research at the Translational Genomics Research Institute (TGen). Today, molecular profiling and other genetic testing technologies have become powerful tools for doctors to match patients with personalized therapies for their cancers. With the rapid adoption of genetic testing technology in hospitals, we will see more successful cases like this in the future. Precision medicine combined with immunotherapy provides a better treatment option for untreatable or uncontrollable cancers under standard therapies. Reference: PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer. The New England Journal of Medicine, June 23, 2022.