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

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Descriptive Information
Brief Title † Analysis of the Role of Hepatocyte SLAMF3 Receptor and Drug Resistance Proteins (MDR) in Resistance to Treatment With Sorafenib in CHC Patients
Official Title † Analysis of the Role of Hepatocyte SLAMF3 Receptor and Drug Resistance Proteins (MDR) in Resistance to Treatment With Sorafenib in CHC Patients
Brief Summary 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 molecules whose expression increases in the cancer cell and ensures the repression of chemotherapy molecules outside the target cancer cell. This family includes the proteins ABCG2, MDR and MRP1. Our in vitro studies show that treatment of CHC Huh-7 cells with Sorafenib (10 mM) induces the specific expression of the transcripts of the MRP-1 protein without any effect on the expression of the ABCG2 and MDR protein. In addition, sorafenib has an effect on the expression of hepatocyte SLAMF3 receptor transcripts, a receptor recently identified in hepatocyte tissue. Indeed, it has been shown that the expression of SLAMF3 is lowered in the cancerous tissue compared to the healthy tissue and that the reintroduction of a strong expression in the cancer cell inhibits its proliferation by inhibiting the MAPK Erk pathway, Cancer cells to apoptosis and inhibits the uptake of tumor masses in the Nude mouse (I. Marcq, et al., 2013).
Detailed Description
Study Phase N/A
Study Type † Observational
Study Design †
Primary Outcome Measure † Rate of expression of SLAM3 and MDR transcripts, correlation with the responder status or not with Sorafenib
Secondary Outcome Measure †
Condition † Hepatocyte Receptor Hepatocellular Carcinoma
Intervention † OtherStudy on samples of tumor and peri-tumor tissues from patients with hepatocellular carcinoma
Study Arms / Comparison Groups Patients with untreated CHC not sorafenib Patients with non-sorafenib CHC Patients with CHCs responding to sorafenib
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Other
Estimated Enrollment † 0
Start Date † November 20, 2015
Completion Date November 20, 2016
Primary Completion Date November 20, 2016
Eligibility Criteria † Inclusion Criteria: - Patients over 18 years of age, - Diagnosis of hepatocellular carcinoma (histological or non-invasive criteria of Barcelona), Group 1: Tumor and peri-tumor tissue samples from patients with untreated CHCs sorafenib - Patients who received treatment other than sorafenib (chemo-embolization, radiofrequency, resection, ...), Group 2: Tumor and peri-tumor tissue samples from patients with non-sorafenib CHC - Patients treated with sorafenib, - Patients not responding to treatment with sorafenib Group 3: Tumor and peri-tumor tissue samples from patients with CHCs responding to sorafenib - Patients treated with sorafenib, - Patients responding to treatment with sorafenib Exclusion Criteria: - Age
Gender All
Ages 18 Years - N/A
Accepts Healthy Volunteers
Contacts ††
Location Countries † France
Administrative Information
NCT ID † NCT03113604
Organization ID PI2015_843_0021
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † Centre Hospitalier Universitaire, Amiens
Collaborators ††
Investigators † : ,
Information Provided By
Verification Date April 2017
First Received Date † April 10, 2017
Last Updated Date April 10, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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