Therapeutic innovation and regenerative medicine in cardio-oncology

Supervisors: Dr. Canan NEBIGIL & Dr. Laurent DESAUBRY

Overview

Cardiotoxicity is one of the major adverse effects of anticancer drugs, impacting both the completion of treatment and short- and long-term quality of life. Cardio-oncology is an emerging medical field focused on the prevention, detection and treatment of cardiovascular effects caused by anticancer therapy.

Our topic, which is part of the European ERA-NET consortium in cardio-oncology, combines medicinal chemistry, molecular and cellular biology, as well as pharmacology to address the following objectives:

  1. Develop new non-peptidic cardioprotective agonists targeting the prokineticin receptor 1 (PKR1),

  2. Discover new ligands for prohibitins and inhibitors of the translation initiation factor eIF4A for the treatment of cardiac diseases and cancers,

  3. Develop new diagnostic tools for cardiotoxicity,

  4. Identify the molecular and cellular mechanisms controlling cardiac myogenesis, neovascularization and adipogenesis in hearts damaged by anticancer drugs (e.g. anthracyclines, cisplatin). 

The biological and medicinal chemistry studies are supervised by Dr. Canan Nebigil and Dr. Laurent Désaubry, respectively.

Innovative and emerging projects

  • Development of new anticancer drugs targeting prohibitins,

  • Development of new anti-metabolic and cardioprotective drugs targeting prokineticin receptors,

  • Identification of new mechanisms and therapeutic targets involved in the cardiotoxicity of anticancer drugs,

  • Discovery of early epigenetically regulated biomarkers for the diagnosis and prognosis of cardiotoxicity in breast cancer patients,

  • Identification of mechanisms and biomarkers in cohorts of heart failure patients, as well as using 3D cardioids and organoids,

  • Regenerative medicine and tissue engineering based on miRNA and LnDNA.

Key achievements (completed or ongoing)

  • Identification of new prohibitin ligands and eIF4A inhibitors for the treatment of cancers and inflammatory disorders,

  • Discovery of the role of the prokineticin pathway in the development of epicardial adipose tissue (EAT) and EAT-associated cardiomyopathy,

  • Identification of potential pharmacodynamic biomarkers for the efficacy of doxorubicin in overcoming resistance in multicellular breast cancer spheroids,

  • Identification of the contribution of pressure overload induced by prokineticin receptor 2 (PKR2) to the development of hypertrophy and endotheliopathies,

  • Discovery of the first prokineticin receptor-1 agonist that inhibits anthracycline-induced cardiovascular toxicity through myocardial and vascular protection.

Scientific expertise

  • Cardio-oncology

  • Cellular and molecular biology

  • Cardiovascular and metabolic physiology

  • Pharmacology

  • Medicinal chemistry

  • Bioorganic chemistry