Centre Méditerranéen de Médecine Moléculaire, Nice
The melanoma, a malignant tumor developed from melanocytes is one of the most lethal cancers among young adults. The prognosis of metastatic melanoma is extremely pejorative. Even if recently encouraging results were obtained with BRAF inhibitor and immunotherapy, responses are transitory. Thus, it appears necessary to develop new approaches enabling the discovery of new drug candidates for specific biotherapy treatment of melanoma. In collaboration with chemistry team, we selected candidate exhibiting strong death-promoting effects in melanoma cells using structure activity relationship studies. We identified the GRP78 (BIP) an endoplasmic reticulum protein, as the target. We demonstrated that the potential interaction between our compound and GRP78 increases Endoplasmic Reticulum Stress and leads to melanoma cell death by autophagy and apoptosis mechanisms. Moreover, endoplasmic reticulum stress has already been involved as a drug resistance mechanism in melanoma suggesting an interest to combine those new molecules with already used therapies in melanoma.
Host: Prof. Christian Widmann