Médecine de précision pour le cancer du sein triple-négatif

 

Saima Hassan

Centre hospitalier de l'Université de Montréal [CHUM]

 

Domaine : cancer

Programme Chercheurs-boursiers cliniciens - Junior 1

Concours 2018-2019

Partenaire :

Fondation du cancer du sein du Québec

Breast cancer is one of the most common cancers affecting Canadian women. Triple-negative breast cancer has a poorer overall survival than other breast cancer subtypes, and is currently treated with three or four types of chemotherapy.  Lacking expression of two hormone receptors and a growth factor receptor, triple-negative breast cancer patients could benefit from therapy that targets specific molecular aberrations in the tumor that can help improve efficacy and decrease toxicity.  My program focuses on a family of targeted therapeutic agents that affect DNA damage and repair mechanisms: PARP inhibitors. While PARP inhibitors have started to demonstrate efficacy in clinical trials, there still remain several unanswered questions before they can be used in the clinic. 

My program focuses on two main objectives: how to use PARP inhibitors in combination with other therapies, and how to select breast cancer patients that will best respond to PARP inhibitors.   I will evaluate different sequencing strategies of a PARP inhibitor in combination with a DNA-damaging chemotherapeutic, carboplatin, to determine their impact upon spread of cancer to distant organs and toxicity.  My second objective aims to determine the role of genetic and imaging-based predictors of response to anti-PARP therapy using patient tissues that will be implanted in mice. My group has previously identified a collection of 63 genes (signature) that predicted response to a PARP inhibitor. 

I will further test the predictive potential of our gene signature with tumor samples from different patient cohorts using sophisticated computer programs.  Furthermore, I will quantify clusters of a protein biomarker of DNA breaks that will be visualized using a high-resolution fluorescent microscope.  Together, the overarching goal of my program aims to improve the therapeutic approach for triple-negative breast cancer patients by improving their treatment and better selecting patients that may best respond to PARP inhibition.