Nicholas Colangelo, MD, PhD

Amplifying the Effectiveness of FLASH RT in Pancreatic Cancer Treatment

Nicholas Colangelo, MD, PhD, and his colleagues at NYU Langone Health’s Perlmutter Cancer Center are exploring a novel method to treat pancreatic cancer, which has one of the lowest rates of survival. Because the pancreas is located near many important organs, current treatments, including surgery and radiation, are often rendered difficult or impossible. By combining two emerging therapies, Dr. Colangelo hopes to improve care and outcomes for people with pancreatic cancer.

“Radiation treatments for pancreatic cancer are limited by the sensitivity of the bowel. This project seeks to show in a pancreatic cancer model that FLASH radiotherapy (RT) and a class of drugs called superoxide dismutase (SOD) mimetics can shrink tumors and improve survival, while sparing the sensitive bowel,” says Dr. Colangelo.

FLASH RT is a new technology that delivers radiation much faster than current methods and has been shown to reduce radiation-induced damage in healthy tissues while still being effective against cancer. How FLASH RT spares nearby tissues is not well understood, but a proposed explanation is that the faster radiation delivery results in a surge of damage called oxidative stress that overwhelms the cancer cells but is counteracted by mechanisms in the bowel. SOD mimetics are drugs that convert the oxidative stress into a form that is easier for the bowel to handle but tougher for the cancer to manage, potentially making FLASH RT even more effective.

Dr. Colangelo’s team is conducting preclinical research to investigate combining FLASH RT and SOD mimetics to optimize treatment for pancreatic cancer. With a James D. Cox Research Award from the ROI, they are:

• Examining how healthy cells are spared by comparing damage caused by oxidative stress in bowel and pancreatic cells treated with FLASH RT versus conventional radiation therapy and with or without SOD mimetics.
• Demonstrating that combining FLASH RT and SOD mimetics reduces pancreatic cancer cell survival compared to conventional radiation therapy.
• Establishing that SOD mimetics can reduce bowel toxicity, decrease tumor size and improve survival in pancreatic cancer.

The current five-year survival rate for pancreatic cancer is 12% and new treatment approaches are critical to enhancing outcomes. If successful, Dr. Colangelo’s groundbreaking research on combining FLASH RT and SOD mimetics has the potential to eventually transform care for people with pancreatic cancer and improve survival rates.

The James D. Cox Research Award is a special recognition for a resident pursuing a career in research that is generously supported by Ritsuko Komaki-Cox, MD, FASTRO.