The Lung Cancer Research Foundation announces its partnership with the Israel Cancer Research Fund on a project led by Joel Yisraeli, Ph.D., and his lab in the Department of Developmental Biology and Cancer Research at the Hebrew University of Jerusalem. The LCRF-ICRF project grant is a three-year, $180,000 award.
The project, “Treating Lung and Colorectal Carcinomas by Targeting IGFBP1,” will study the effects of an IGF2BP1 inhibitor discovered by Yisraeli and his team, building upon previous ICRF-funded research.
IGF2BP1 is a protein that binds to RNA and is usually active before birth, but it becomes active again in many types of cancers. In patients with lung adenocarcinoma, those with high levels of IGF2BP1 and a mutated KRAS gene have a much lower survival rate (15 months) compared to those without high levels of IGF2BP1 (88 months). In mice, when IGF2BP1 is active along with the mutant KRAS gene, it helps tumors grow in the lungs and spread to other parts of the body. However, blocking IGF2BP1 can prevent these tumors from spreading.
Yisraeli’s lab discovered and refined a molecule called “AVJ16,” which prevents IGF2BP1 from attaching to KRAS and other cancer-promoting RNAs. In mouse models, this drug stops cancer cells from growing when injected under the skin. This project will allow Yisraeli and his team to test AVJ16 in a genetic mouse model of lung cancer, explore its potential as an additional therapy, and develop a small molecule that targets and degrades IGF2BP1.
Their ultimate goal is to create a set of powerful new therapies that specifically inhibit IGF2BP1 and prevent cancer development. They hope these animal studies will be the first step toward a clinical trial.
KRAS is the most common mutation in non-small cell lung cancer patients, making up about 25% of all lung cancers. The KRAS gene serves as a signaling pathway for cell growth, and when there is a mutation in the KRAS gene, it causes excess signaling, leading to excess cell growth and cancer. Roughly half of patients with KRAS-mutated lung cancer have a KRAS G12C mutation, for which there are targeted drug therapies following progression after first-line treatment. However, because these agents are not curative nor active in other KRAS mutations, additional research is urgently needed.
Professor Yisraeli has received previous grant funding from ICRF over the years, including when he initially set up his lab at the Faculty of Medicine at Hebrew University after returning from a post-doctoral fellowship in developmental biology at Harvard University. This support has enabled new discoveries and paved the way for his current lung-cancer research.
“LCRF is delighted to partner with ICRF on this research project,” says Antoinette Wozniak, M.D., LCRF’s chief scientific officer. “In a notoriously difficult cancer to treat, this project explores a promising new target for KRAS-mutated lung cancer, which is an exciting development.”
“I’m grateful for this powerful partnership between ICRF and LCRF,” says Arnold Baskies, M.D., FACS, chair of ICRF’s board of trustees. “Our collaboration amplifies our shared vision to advance lung cancer treatment while leveraging Israel’s innovations in the fight against cancer.”
To learn more about LCRF and its grants program, visit LCRF.org. To learn more about ICRF and its research program, visit icrfonline.org.