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Fabrice André, MD, PhD
Research Director, Head of INSERM Unit U981
INSERM (Institut National des Sciences et de la Recherche Médicale)
Associate Professor, Department of Medical Oncology
Institut Gustave Roussy
Seeking to identify genetic biomarkers that predict response to a class of targeted drugs called mTOR inhibitors.
Conducting analyses of metastatic breast cancers to identify genomic alteration associated with poor outcome to design new combinations to improve response
These studies are advancing precision medicine by identifying novel approaches to prevent resistance to mTor and other targeted therapies.
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.
mTOR regulates protein synthesis in cancer cells. mTOR inhibitors improve outcome in patients with ER+/HER2- metastatic breast cancer, but the response varies. The goal of Dr. Andre's BCRF project is to identify genetic biomarkers that predict which patients will show the greatest response to mTOR inhibitors.
Preliminary data suggest that mTOR activation and the number of mutations in cancer cells predict the benefit from these inhibitors. His group is analyzing the DNA from metastatic breast cancer patients to determine whether multiple DNA mutations within the different tumor cells make the tumors resistant to therapy. They have collected samples from 110 patients treated with the mTOR inhibitor, everolimus, and performed molecular analyses on these samples.
In the coming year, Dr. Andre' will analyze the genome in 300 patients with metastatic breast cancer to identify new targets that are specific to metastases, determine whether they can be targeted with new therapies, and work to uncover the molecular mechanisms that create mutations in metastatic tumors.
These studies will lead to better personalized therapies by identifying new genes involved in drug sensitivity and resistance in patients with metastatic breast cancer.
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.