Monday, June 11, 2018

Team "Tumor Hypoxia and Metabolism" receives a donation

GEMLUC donation to the Research Team led by Jacques Pouyssegur, Research Director Emeritus of the CNRS

Validation of new targets against Pancreatic Cancer

The team "Hypoxia and tumor metabolism" led by Dr Jacques Pouyssegur at the CSM, internationally renowned in the field of hypoxia and tumor metabolism, seeks to validate by genetic potential new anti-cancer targets. Their research, supported by the GEMLUC, Group of Monegasque companies in the fight against cancer, focused on pancreatic cancer, which is the most aggressive and lethal cancer for which Medicine is failing.
Cancer cells protect themselves from lethal oxidative stress by the increased production of a major cellular antioxidant, "Gluthation". The synthesis of Gluthation requires 3 amino acids including Cysteine. By disabling the xCT gene, a specific cystine transporter (precursor of cysteine), the researchers obtained on 2 types of pancreatic cancer cell lines (Capan-2 and MiaPaca-2) a collapse of Glutathione and a lightning cell death by abolition of antioxidant defenses.

© CSM
Gemluc donation of 140 000 € to the "Hypoxia and tumor metabolism" team of the CSM on 16 March 2018. From left to right: Pr Patrick Rampal, Mr. Maurice Gaziello, Ms. Boutaina Daher, Dr. Jacques Pouysségur, Dr. Milica Vucetic, Mrs. Marie Gramaglia, Mr. Eric Heremans and Mrs. Jasmine Kafafian

 

Why this discovery could lead to anti-cancer exploitation? 

Normal cells, unlike cancer cells, have no or very low levels of 'oxidative stress' that can withstand the inhibition of the Cystine transporter. Conversely, cancer cells have a very high level of oxidative stress which, moreover, is magnified by conventional chemotherapy. So, combining the inhibition of the cystine xCT transporter with chemotherapy over short periods of time can bring a considerable benefit to these aggressive cancers.
These first advances supported by GEMLUC were presented at several international conferences in 2017-18 on oxidative stress, by Milica Vucetic, post-doctorant, Boutaina Daher, PhD student, and upon invitation by J. Pouysségur in Spain, Austria, South Korea (Ulsan), Japan (Osaka, Kyoto) and China (Beijing).
This team is one of the first to have exploited the technique of CRISPR-cas9 developed by Emmanuelle Charpentier (molecular scissors of DNA, see the remarkable article of the Point, n ° 2374, March 2018). The GEMLUC-supported team has isolated and characterized nearly 40 mutants thus validating a number of new anti-cancer targets.

© LE POINT
Scheme issued from publication Le Point n°2374, March first 2018 - Médecine Les Prodiges de la génétique


For more information, see www.centrescientifique.mc or contact:

Dr Jacques Pouysségur, Research Director Emeritus CNRS / CSM Team Leader of the 'Tumor Hypoxia and metabolism', Medical Biology Department, Centre Scientifique de Monaco (Jpouyssegur@centrescientifique.mc).