Previously Funded Research

Francisco Expósito, PhD

Yale University

Research Project:

Investigating novel synthetic lethal vulnerabilities in EGFR-driven lung cancer

Summary:

Lung cancers driven by mutations in EGFR represent between 15-60% of lung adenocarcinomas. The presence of EGFR mutations predicts the response to specific therapies referred to as tyrosine kinase inhibitors (TKIs). Although these inhibitors have revolutionized the way we treat this type of cancer, patients have varied responses and eventually, all tumors will become resistant and stop responding, highlighting the need for alternative treatment options.

In this project, we aim to understand how the loss of SETD2 hinders EGFR-driven tumor growth to leverage these findings to create new precision treatments for the treatment of patients with EGFR-mutant tumors.

This project was awarded the LCRF William C. Rippe Award for Distinguished Research in Lung Cancer, acknowledging the investigator whose proposal not only demonstrated exceptional scientific merit but also exemplified an enduring commitment to making an impact in the field of lung cancer research.

I am really honored to receive the William C. Rippe Award for Distinguished Research in Lung Cancer from the Lung Cancer Research Foundation. Thanks to the support from LCRF we hope to uncover novel genetic vulnerabilities of EGFR-driven lung tumors and leverage these findings to implement and inform new precision-based treatments for this type of tumors in the future.

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1-year update: spring 2025

What he’s doing:
Dr. Expósito is investigating a promising new approach to treating EGFR-driven lung cancer by studying the role of SETD2, a gene that normally helps suppress cancer formation. When SETD2 is lost, cancer growth can accelerate, particularly in EGFR+ lung adenocarcinoma.

How it’s going:
To better understand this process, Dr. Expósito has developed advanced genetic models that allow researchers to deactivate and restore SETD2 in cancer cells. His team is now preparing to study SETD2 in human tumor samples, which could provide critical insights into how manipulating this gene may create new therapeutic opportunities. His team is now preparing to study SETD2 in human tumor samples, which could provide critical insights into how manipulating this gene may create new therapeutic opportunities.

What it could mean for patients:
If successful, this research could lead to innovative strategies for targeting EGFR-mutated lung cancer, offering new hope for patients in need of better treatment options.