From solving the mystery of virus-specific immune cells in tumors to advancing surgical techniques, more than a dozen new cancer research Pilot Projects are off the ground, thanks to record-breaking community fundraising at last year’s Prouty. Part 1 sheds light on seven of the projects. But there is much more action in the labs:
Oxygen dynamics in radiation
Ultra-high dose rate radiation, also called FLASH, appears to be able to eliminate all tumor cells without excessive damage to the surrounding normal tissues. One theory is that this effect is due to the depletion of oxygen, which reduces DNA damage in the normal tissue. Cancer researchers Lesley Jarvis, MD, PhD, Arthur F. Petusseau, PhD, and P. Jack Hoopes, DVM, PhD, are investigating this theory by using a natural molecule called PpIX to measure oxygen levels in skin models during radiation therapy. This quick and non-invasive laser light technique can collect essential oxygen depletion data to better understand the FLASH effect compared to standard radiation therapy approaches.
Earlier treatment for some leukemia patients
Up to 80% of people with Chronic Lymphocytic Leukemia (CLL) do not have symptoms and are not eligible for treatment. Instead, they are closely monitored. However, nearly half of these patients will progress to later-stage disease that requires treatment and can have poor outcomes. While early treatment has not been shown to improve survival, some patients may benefit from it. But which ones? Researchers Prabhjot Kaur, MD, Brock C. Christensen, PhD, and Lauren M. Wainman, PhD, believe that certain genetic markers and epigenetic profiles could help identify which patients in this “watch and wait” period are at risk of progression and would benefit from early treatment. Their precision medicine Pilot Project aims to measure molecular signatures, which will be used to improve treatment and outcomes for CLL patients.
Better diagnostics for a common pediatric cancer
Neuroblastoma is the most common cancer in infants, with a high incidence in the northeastern U.S. A key genetic marker called MYCN—a driver of tumor growth and treatment resistance—is amplified in 25 to 30 percent of neuroblastoma cases and is associated with poor prognosis. Therefore, it is crucial to identify this mutation for accurate diagnostics and effective treatment. Chun-Chieh Lin, MD PhD, and John X. J. Zhang, PhD, developed an ultrafast sequencing platform that can detect such mutations throughout the genome in just 2.5 hours, costing only $125 per sample. With Prouty funding, they will compare their platform to existing diagnostic methods to determine its accuracy and potential to become the new standard of clinical care. The team will also use a highly sensitive system to purify and analyze MYCN to better understand its role in neuroblastoma and other tumor types.
Pushing back on melanoma treatment resistance
Melanoma is the deadliest form of skin cancer. More than half of melanoma patients have a mutation called BRAF that drives tumor growth. Treatments that inhibit BRAF only work for a limited time before immune suppression and resistance to therapy become a problem. Researchers Patricia Pioli, PhD, and Li Song, PhD, have identified a drug that reduces immune suppression in tumors. Interestingly, the drug is only effective in later-stage tumor growth. The team believes that this is because of changes in the tumor microenvironment that occur over time. In their Prouty Pilot Project, they hope to clarify, for the first time, how the immune tumor landscape changes as tumors become resistant to BRAF inhibitors. They will also study changes in immune cell activation, which could lead to the discovery of therapeutic targets for combatting BRAF inhibitor resistance.
Where did they come from?
Exposure to infections and to vaccines generates immune T cells that retain 'memory' and patrol the body for reinfection. In addition to circulating through blood and lymph fluid, it is now known that these infection-fighting cells also reside within tissues. Surprisingly, T cells specific for common viruses such as influenza A were found in a wide range of tumors with no known viral origin, including brain tumors, where immune infiltration has historically been thought of as restricted. This prompts an intriguing question that researcher Pamela Rosato, PhD, and mentor Mary Jo Turk, PhD, will address with their Prouty grant: where did they come from? Addressing the origin of virus-specific T cells in brain tumors will open doors to harnessing these cells in new immunotherapies.
Nerve-sparing sarcoma surgery with fluorescence
Curing soft-tissue sarcomas requires surgical removal of the entire tumor along with a margin of healthy tissue surrounding the tumor. Surgeons rely on medical imaging, visual cues, and touch to determine margin thickness. Sometimes there are critical nerves touching the tumor. This requires surgeons to choose between nerve sacrifice, resulting in functional difficulties for patients, or nerve preservation, increasing the odds of cancer-positive margins and local cancer recurrence. The team at Dartmouth Cancer Center has special expertise in tumor- and nerve-specific fluorescence imaging. Researchers Samuel S. Streeter, PhD, and Kimberley S. Samkoe, PhD, in collaboration with Oregon Health & Science University, will, for the first time, combine these capabilities to advance nerve-sparing sarcoma surgery without additional risk to patients.
Registration for Prouty 2024 is open! The event will take place Saturday, July 13, 2024. To contribute to cancer research projects such as these and many more, get involved in The Prouty today.