Marseilles, France, October 31, 2016 -Genoscience Pharma, a company focused on discovering and developing small molecules to treat cancer by targeting cancer stem cells, today announces that it will present data on its most promising candidate at The Liver Meeting® 2016: November 11 – 15, Boston, USA
The details for the data presentations at AASLD are as follows.
Title : Preclinical characterization of a novel first in class GNS561: autophagy inhibitor therapeutic candidate for treatment of hepatocellular carcinoma
Publication Number: Poster n.313, page 162A, HEPATHOLOGY, Oct. 2016
Background: In spite of successful approval and wide application of sorafenib, the prognosis for patients with advanced hepatocellular carcinoma (HCC) remains poor. In recent years, highly tumorigenic sub‐populations of cancer cells named Cancer Stem Cells (CSCs) have been implicated in post‐treatment tumor recurrence. Indeed, CSCs are resistant to chemotherapy, and they have the ability to regenerate all the cell types within the tumor. For this reason, innovative drugs with original mechanism of action which tackle CSCs would likely improve cancer treatment of patients.
Material and methods: Antitumor activity of GNS561 was tested on a panel of cancer cell lines. Its effect on HCC CSCs subpopulation was assessed by flow cytometry (ALDH activity, CD133 expression) and by sphere formation assay. Tolerance and plasma and liver pharmacokinetic were evaluated after single and repeated dosing in mice and rats. In vivo GNS561 activity was tested in orthotopic mouse models.
Results: GNS561 demonstrated autophagy inhibition and apoptosis induction activities related to lysosome disruption. It showed potent antitumor activity against a panel of human cancer cell lines. In HCC cell lines, GNS 561 was active on both whole populations (mean EC50 2μM) and subpopulations displaying CSC features (high ALDH and CD133 positivity). Further, GNS561 was effective against a panel of HCC tumors even from patients harboring sorafenib resistance. In mouse, GNS561 was found well tolerated and highly selectively trapped in the liver (exposure ratio liver/plasma about 170 animals), and showed a significant tumor growth inhibition in orthotopic HCC mouse models.
Conclusions: Our results provide a rationale for testing autophagy flux disruption as a novel therapeutic strategy for HCC. GNS561 is a liver selective drug active against both the whole tumor bulk and CSCs, which offers great promise for HCC treatment.
Hepatocellular carcinoma (HCC), Resistance, Cancer, Lysosome, Autophagy, Liver