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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
Goal: To improve response to targeted breast cancer therapies by identifying strategies that prevent resistance.
Impact: Dr. André has launched a clinical trial to study how tumors develop resistance to a drug called alpelisib that targets the PI3K pathway, which has been shown to play a role in the progression of breast cancers in nearly a third of patients. His findings could help identify new approaches to prevent resistance to alpelisib and other drugs in its class.
What’s next: Dr. André and his team will measure the level of gene activity in breast cancers before and after treatment with alpelisib. This comparison could yield new insights into how resistance develops.
Targeted therapies such as alpelisib are promising treatment options for many patients with breast cancer. But because no two breast cancers are alike, response to treatment varies. Dr. André is pursuing ways to identify genetic markers associated with poor response to targeted therapy, which could help predict which patients are most likely to benefit the most from alpelisib and other drugs like it.
Full Research Summary
Research area: Identifying genomic alterations associated with poor response to targeted therapy.
Impact: Dr. André’s work has the potential to advance precision medicine in three ways:
- Understanding which molecules are involved in the resistance to a therapy;
- Identifying which patients benefit the most from targeted therapies using the markers of resistance he and his team discover;
- Improving patient outcomes by using combination therapies designed to prevent or overcome resistance.
Current investigation: With the support of BCRF, Dr. André has launched a clinical trial aimed at discovering mechanisms of resistance to alpelisib, a new PI3K (phosphatidyl inositol -3 kinase) inhibitor approved by the FDA. P13K, a key protein in the progression of breast cancers, is a promising therapeutic target. However, studies suggest that some patients develop resistance to PI3K inhibitors like alpelisib. This may help explain why the promise of this targeted therapy has not translated into improved patient outcomes.
What he’s accomplished so far: Dr André has performed the largest genomic analysis of metastatic breast cancers to date.
What’s next: He will now analyze the genome of cancer cells before and after treatment with alpelisib. Comparing the two may reveal mechanisms of resistance and inform the development of novel approaches to prevent it from occurring.
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.