RTICC Search Committee Candidate Seminar- Asael Roichman

Dr. Asael Roichman
Princeton University

"The Interplay between Diet, Gut Microbiota and Cancer Therapy"

Diet can profoundly influence cancer therapy, yet the mechanisms linking specific dietary components to therapeutic efficacy remain unclear. To investigate this, I studied phosphatidylinositol 3-kinase (PI3K) inhibitors, which show limited efficacy in human solid tumors. In murine models, PI3K inhibitor activity is dramatically enhanced by a ketogenic diet, previously attributed to dietary suppression of insulin. I confirmed this enhancement but surprisingly found it to be unrelated to diet macronutrient composition, glycemia, or insulin. Instead, the diet–PI3K interaction involves microbiota metabolism of ingested phytochemicals. Specifically, the murine ketogenic diet is a purified formulation that lacks the complex spectrum of phytochemicals present in standard chow, including the soy phytochemicals soyasaponins. These compounds are converted by the gut microbiota into inducers of hepatic cytochrome P450 enzymes, which accelerate PI3K inhibitor clearance and reduce drug efficacy. A high-carbohydrate, low-phytochemical diet, as well as antibiotics that suppress the gut microbiota, enhance PI3K inhibitor activity in mice. These findings reveal a phytochemical–microbiota–liver axis that modulates systemic drug levels and efficacy.

I also examined whether dietary fiber enhances immune checkpoint blockade (ICB), as suggested by clinical studies, and found that fiber content alone had limited and inconsistent effects on ICB efficacy across tumor models—suggesting that other dietary factors correlated with fiber intake, possibly phytochemicals, may underlie observed clinical associations. These studies highlight the importance of considering dietary phytochemicals and microbiota when evaluating drug exposure, therapeutic efficacy, and inter-individual variability in treatment response.

One of the crucial RTICC goals is the recruitment of talented and established faculty from all relevant disciplines who strive to make an impact on cancer research. The RTICC is pleased to host a candidate seminar featuring Dr. Asael Roichman, a postdoctoral fellow at Princeton University. This seminar offers an opportunity for the RTICC community to engage with a prominent researcher in the field, ask questions, and learn more about Dr. Roichman’s potential contributions to our mission. We encourage all members of the RTICC to attend and participate in this seminar.

Following the seminar at 13:00-14:00, there will be a Chalk Talk in the 11th floor seminar room, Rappaport Faculty of Medicine. The chalk talk is a closed event for Principal Investigators only.