Novel metallic complexes for with radiosensitizing properties in cancer research: Biochemical and Biological evaluation
Project: Novel metallic complexes for with radiosensitizing properties in cancer research: Biochemical and Biological evaluation
Laboratory: Chemistry, Modelling and Imaging for Biology, Institut Curie
Affiliation: Institut Curie Orsay, CNRS UMR9187, INSERM U1192
Address: Université Paris Sud, Batiment 100-112. Rue Henri Becquel. 91405 Orsay
Name: Marie-Paule Teulade-Fichou
Phone number: +33169863086
Name: Sophie Bombard
Phone number: +33169863189
Subject Keywords: metallic complexes, G-quadruplexes, radiation, radiosensitization
Summary of lab’s interests: The laboratory’s interest is to design new compounds or metallic complexes in order to target specific DNA structures that are called G-quadruplexes. The present proposition is based on a recent research on the screening of the potent radiosensitising properties of such compounds. Among them, we discovered different series of metallic complexes with diverse anchorage to DNA.
Project summary: An important strategy in cancer therapeutics is to increase tumor sensitivity to radiotherapy. Different radiosensitizing chemotherapeutic drugs exist among which some are DNA-binding drugs, such as G-quadruplex (G4) binding ligands. G4 structures can be formed from G-rich DNA sequences. Growing evidence states that G4s can form on various regions of genomic and telomeric DNA, hence controlling several biological processes and are considered as valuable targets for anti-cancer therapy. The project is is based on recent results from our laboratory showing that some metall complexes (some targeting G4), are radiosensitizers on various cancerous cell lines. Our results indicate that radiosensitization potential doesn’t correlate to specific metals, ligand structures or binding mode of the drug to DNA but could interfere with the DNA damage repair mechanism. The aim of the project is to decipher the mechanism of action underlying their radiosensitizing effect. The biochemical and biological properties, in combination with radiation, will be evaluated and a structure activity relationship in terms of biological targets and/or DNA anchorage will be established allowing optimization of these new complexes
Interdisciplinary aspect of the project: The project is interdisciplinary since it involves chemistry of new metallic complexes designed in our laboratory together with our collaborators (ICSN in Gif sur Yvette),biophysics , biochemistry and biology of these complexes in combination with radiations. The student will acquire an interdisciplinary education from biochemical and biophysical evaluation of the new complexes before their cellular evaluation to decipher their underlying radiosensitizer effect.
Funding: The PhD student will apply for the funding from the doctoral school