Research Summary: Folate-related biomarkers as predictors of response to pemetrexed therapy

Grant Recipient: Dr. Alexander Steven Whitehead
Title of Project: Folate-related biomarkers as predictors of response to pemetrexed therapy
Sponsoring Institution: University of Pennsylvania

Folate is a B vitamin that is very important for maintaining health and for protecting against a range of major diseases. It is obtained as ‘natural’ folate from food, in particular leafy green vegetables, or as the synthetic form folic acid from supplements and products made with fortified flour. There are genetic differences in the enzymes that control the way that folate is used inside cells; folate is actually present as multiple forms that support different biochemical processes, and these differences confer different levels of susceptibility to diseases that are associated with low folate and altered folate metabolism. Some of the genetic differences have been linked to lung cancer, and some have recently been linked to good responses to pemetrexed, an anti-folate drug that is used to treat lung cancer. The goal of this project is to define the main folate-related genetic variants AND the relative amounts of the different forms of folate inside cells in patients with lung cancer, and to establish whether any of these factors are over-represented in (i) lung cancer patients compared to healthy individuals, and, even more importantly, in (ii) lung cancer patients who show superior responses to pemetrexed. The project has the potential to identify genetic markers and/or biomarkers that could be used to guide lung cancer chemotherapy.