Analysis of the Role of Hepatocyte SLAMF3 Receptor and Drug Resistance Proteins (MDR) in Resistance to Treatment With Sorafenib in CHC Patients

Primary liver cancer or hepatocellular carcinoma (HCC) is the 7th most common cancer in humans; 9th in women (figures from the Association for Research against Cancer ARC). This cancer is a major public health problem on a global scale. Patients, whose diagnosis is often late, are at advanced stages of the pathology, even those who benefit from locoregional treatments have a poor prognosis and suffer from a lack of curative therapeutic strategies. CHC is highly refractory to cytotoxic chemotherapy and so far the response rates to conventional systemic chemotherapy has provided a clinical benefit where survival was prolonged by more than 25% in patients with advanced CHC. Further efforts are needed to effectively manage HCC. Knowledge of the mechanisms regulating proliferation and inhibiting the sensitivity of transformed cells to apoptosis is the key to the development of more effective therapeutic strategies. Several new therapies, called targeted therapies, are tested in clinical trials. Currently, the most effective molecular agent for targeting the Raf pathway is sorafenib capable of also inhibiting tyrosine kinases of VEGFR and PDGFR. Sorafenib, a multikinase inhibitor, decreases the proliferation of tumor cells in vitro that inhibit the activity of targets present in tumor cells (CRAF, BRAF, V600E BRAF, c-KIT, and FLT-3) and tumor vascularization VEGFR-2, VEGFR-3, and PDGFR-beta). Despite the real benefit of this treatment, its efficacy (three months of overall survival) and its indication remain limited to Child-Pugh A, WHO 0-2 patients in whom curative treatment is contraindicated. In addition, several patients have resistance to Sorafenib and thus find themselves in therapeutic failure, thus limiting the therapeutic choice for these patients. Resistance to treatment with Sorafenib limits the therapeutic choice. The mechanisms responsible for this resistance remain to be elucidated. Drug resistance proteins, MDR Multi-Drug Resistance, is a family of molecu