Alberto Ciccia, PhD
2024 Collaborative Research Development Grant
Columbia University
Defining the impact of DNA repair variants on immune-based therapy of ovarian cancer at scale
Project Summary
Very few women with high-grade serous ovarian cancer (HGSOC) are successfully treated, and their lifespan after diagnosis is often months. We are working to increase success rates by identifying tools to improve existing treatments so they work better for patients. Treatments include PARP inhibitors (PARPi) and immune checkpoint blockade (ICB).
Tumors have damaged DNA, and they fix it through a DNA repair pathway called homologous recombination (HR). The HR pathway, however, is defective or broken in about half of HGSOC cases. Specific effects of most individual HR gene mutations on tumor growth and treatment are unknown.
To shed light on this issue, three research groups will integrate their expertise in DNA/genome stability (New York), HGSOC biology (Milan), and HGSOC-related immunotherapy (Chicago). Cutting-edge technologies will be applied to screen >22,000 HR gene mutations in a model system using cells from patients. This system will be used to identify specific mutations that affect HGSOC responses to PARPi and ICB. The clinical importance of our research will be defined by analyzing samples and data from a recent clinical trial on HGSOC patients treated with PARPi + ICB.
Our goal is to define predictive, HR-related biomarkers that will help identify patients who are more likely to respond to PARPi and ICB. This information could help physicians decide what treatments are best for individual patients and increase success rates of HGSOC treatments.
Bio
Alberto Ciccia conducted his PhD studies in the laboratory of Stephen West at Clare Hall Laboratories and the London Research Institute. In 2007, he started his postdoctoral work in the laboratory of Stephen Elledge at Harvard Medical School. In 2014, he joined the Department of Genetics and Development at Columbia University Irving Medical Center, where he is currently an Associate Professor. His laboratory studies the mechanisms that maintain genome stability using innovative genome editing technologies.