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Fabrice André, MD, PhD
Research Director, Head of INSERM Unit U981
INSERM (Institut National de la Santé et de la Recherche Médicale)
Associate Professor, Department of Medical Oncology
Institut Gustave Roussy
- Seeking to improve response to targeted therapies with strategies to prevent resistance.
- Conducting analyses of metastatic breast cancers to identify genomic alterations associated with poor response to targeted therapy.
- These studies are advancing precision medicine by identifying novel approaches to prevent resistance to an important class of anti-cancer drugs.
No two breast cancers are alike, and treatments don’t work the same for every patient. For patients whose tumors have a specific alteration in a gene or growth pathway, therapies that specifically target those vulnerabilities can more effectively kill the tumor. Unfortunately, many targeted therapies have yielded inconsistent results in clinical trials. Dr. André is conducting a clinical to identify genetic markers in the tumor and blood from patients that may predict response to a class of targeted therapies called PI3K inhibitors.
Full Research Summary
Each breast cancer is characterized by a unique pattern of genomic alterations. Targeting the genomic alteration responsible for transforming cells from benign to malignant should stop cancer progression, but studies suggest that such targeted treatments may lead to drug resistance in some breast cancer patients.
PI3K (phosphatidyl inositol -3 kinase) is a key protein in the progression of breast cancers in about 30 percent of patients, making it a promising therapeutic target. While drugs that target PI3K dramatically decrease the tumor size, they only marginally improve outcome. Understanding why this major effect on tumor shrinkage does not translate into improved outcome could lead to new strategies to prevent or overcome resistance.
Several studies have suggested that resistance to PI3K inhibitors may be due to activation of compensatory pathways that make the targeted therapy ineffective. Dr. André is conducting a prospective clinical trial that aims to identify molecular predictors of benefit and mechanisms of to PI3K inhibitors.
The trial will include patients with ER-positive metastatic breast cancers, whose tumors harbor mutations in the PIK3CA gene. These mutations are known to increase the activity of the PI3K pathway. Dr. André will conduct genomic analysis on tissue and blood collected from patients to identify genomic markers that may predict response to PI3K inhibitors.
PI3K inhibitors and other targeted therapies are promising therapeutic options for many patients. Being able to predict which patients are most likely to benefit will ensure that patients receive the right treatments
Fabrice André MD, PhD, is an oncologist based at Gustave Roussy Cancer Cancer, Villejuif, France. He is Professor of Medicine at University Paris Sud. His BCRF research focuses on the characterisation of molecular alterations in metastatic breast cancers. He is leading several prospective trials that aim to show the clinical utility of genomic tests for patients with metastatic breast cancers. He is also leading development of targeted therapies in the same setting. He is the chair of INSERM Unit U981, a research team dedicated to target identification. He is Senior Editor Breast cancer section at Annals of Oncology.