Alex Kentsis, MD, PhD

About Dr. Alex Kentsis, MD PhD

Alexis Kentsis, MD PhD is an oncologist at the Memorial Sloan-Kettering Cancer Center. Dr. Kentsis specializes in leukemias and refractory tumors in children and young adults.

About Dr. Kentsis’ Research

Rhabdoid and epithelioid sarcomas are aggressive tumors affecting children and young adults. Current treatments are inadequate, with chemotherapy-resistant tumors that cannot be surgically removed proving near universally lethal. To help improve outcomes for pediatric patients diagnosed with rhabdoid and epithelioid sarcomas, the Pediatric Cancer Research Foundation awarded Dr. Kentsis a two-year Basic Science Research Grant in 2023.

Rhabdoid and epithelioid sarcomas are characterized by inactivation of the SMARCB1 tumor suppressor gene, a key regulator of gene expression. Inactivation of the BAF complex through SMARCB1 loss causes uncontrolled gene expression that requires PRC2 and its protein enzyme EZH2. Based on this information, Dr. Kentsis’ colleagues recently completed the first clinical trial of the EZH2 inhibitor tazemetostat, leading to its FDA approval. However, only a subset of patients received a benefit from this therapy.

In two preliminary studies, Dr. Kentsis has identified EZH2-dependent and independent mechanisms of resistance, establishing reliable experimental models to elucidate these molecular mechanisms. Dr. Kentsis aims to define the link between epigenetic dysregulation and fundamental developmental programs in childhood sarcomas. These studies are expected to lead to new rational targeted epigenetic combination therapies to restore healthy gene expression.

Dr. Kentsis has already identified two combination therapies with synergistic anti-tumor activity in cellular models. Together with his team, Dr. Kentsis is investigating these therapies in vivo as a prelude to their translation to clinical trials for patients.