Search for Precision Treatments for BRG1-Deficient Lung Cancers

A recent study showed that the new ATR-blocking drugs killed BRGI-deficient lung cancer cells in the lab and in mice with implanted lung cancer tumors. 

Grantee: Carla F. Kim, PhD
Institution: Children's Hospital Boston
Area of Focus: Mission Boost
Grant Term: 1/1/2019 to 1/1/2021

Precision medicine is like having a special dart that heads right for the bulls’ eye on a dartboard. Knowing which exact genetic mutation a cancer cell has helps doctors know which treatment is most likely to work.

Right now, there aren’t any approved targeted treatments for a specific mutation in the SMARCA4/BRG1 gene that is found in certain types of lung cancers. These are called BRG1-deficient lung cancers. This mutated gene appears in up to 20% of non-small cell lung cancers (NSCLC).

These lung cancers are also resistant to many standard treatments. That means at least some cancer cells survive after treatment. Until now, it’s been unclear how mutations in the BRG1 gene contributed to drug resistance in this type of lung cancer.

Earlier studies by Carla Kim, PhD and other researchers suggest a potential precision treatment showed promise for NSCLC with BRG1 mutations. In the studies, Kim used drugs that target a protein called ATR and that block, or inhibit, its function.

recent article in Cancer Research described some of Kim’s findings that were supported by her ACS Mission Boost grant. She and her colleagues showed that the new ATR-blocking drugs killed BRGI-deficient lung cancer cells in the lab as well as in mice with implanted lung cancer tumors (called patient-derived xenografts).

Kim is the senior author of the article, and two of her co-authors are also ACS grantees studying lung cancer: Carla Concepcion, PhD, from Boston, and Christine Brainson, PhD, from Lexington, Kentucky.

Why Does It Matter? ATR blockers, or inhibitors, are already being used in Phase 1 (human) clinical trials for other types of cancer. The results from Kim’s study show that that ATR blockers could be an effective treatment for lung cancers with the mutation in the BRG1 gene.

The study’s coauthors also said that other types of cancer with a similar genetic mutation may respond well to treatment with ATR blockers. Those cancers may include endometrial, stomach, and certain rare ovarian cancers. This evidence could help this new treatment for certain hard-to-treat lung cancers move quickly to human clinical trials.

Read the study.