Ignite Creation Date:
2024-05-06 @ 9:55 AM
Last Modification Date:
2024-10-26 @ 12:22 PM
Study NCT ID:
NCT03113604
Status:
WITHDRAWN
Last Update Posted:
2017-04-13
First Post:
2017-04-10
Brief Title:
Analysis of the Role of Hepatocyte SLAMF3 Receptor and Drug Resistance Proteins MDR in Resistance to Treatment With Sorafenib in CHC Patients
Sponsor:
Centre Hospitalier Universitaire Amiens
Organization:
Centre Hospitalier Universitaire Amiens
Study Overview
Official Title:
Analysis of the Role of Hepatocyte SLAMF3 Receptor and Drug Resistance Proteins MDR in Resistance to Treatment With Sorafenib in CHC Patients
Status:
WITHDRAWN
Status Verified Date:
2017-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The study has been stopped because no one is
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SLAMF3
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
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:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None