Your Donations in Action: Adam Jay Grippin, MD, PhD

Although chemoradiation, immunotherapy and targeted therapy have improved outcomes for subsets of non-small cell lung cancer (NSCLC), many patients with treatment-resistant mutations still have limited therapeutic options. Among them are patients with STK11-mutant NSCLC, a common and clinically important molecular subtype associated with loss of LKB1 expression and resistance to chemotherapy, radiation, immunotherapy and targeted therapy.

For his 2024 RSNA Research Resident Grant project, “Restoration of LKB1 Expression To Sensitize Tumors to Chemoradiation,” Adam Jay Grippin, MD, PhD, assistant professor in the Department of Immunology and the Department of Thoracic Radiation Oncology at the University of Texas MD Anderson Cancer Center in Houston, investigated whether therapeutic mRNA could restore LKB1 expression and improve treatment sensitivity in LKB1-deficient tumors.

Dr. Grippin and colleagues used mRNA-loaded small extracellular vesicles to deliver nucleic acids to tumor cells. After developing an LKB1 knockout lung cancer model, the team confirmed that loss of LKB1 function reduced radiation sensitivity and showed that LKB1-deficient tumors were less responsive to chemoradiation than LKB1 wild-type tumors.

“A large part of this effort is focused on using RNA therapeutics to reprogram the immune system and the tumor itself to help these therapies work more effectively,” Dr. Grippin said.

The team also identified broader immune-stimulatory effects of mRNA therapeutics. In a retrospective analysis, patients with NSCLC who received COVID mRNA vaccines experienced a near doubling of overall survival compared to unvaccinated peers. The finding also applied to patients with STK11-mutant NSCLC,

“My hope is that additional work in this area will allow us to increase cure rates and decrease toxicity in many of our patients,” Dr. Grippin said.

Since receiving the grant, Dr. Grippin has completed his residency and launched a research program focused on developing new approaches to advance cancer care treatment.

“Using funds from the R&E Foundation as a launching pad, I have been able to begin what I hope will be a long career developing new treatments that help our patients live longer, healthier lives,” Dr. Grippin said.

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Read our previous Your Donations in Action story.