A new article has been recently published in the #journalofcancer showing that #GNS561, a new #autophagy blocker, offers great promise for #cancer therapy by exterminating both the tumor bulk and the Cancer Stem Cells (#CSC) sub-population. A global phase 1b clinical trial in #liver #cancers was recently completed.
Patients with advanced hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) have a
very poor prognosis due to the lack of efficient treatments. As observed in several other tumors, the effectiveness of treatments is mainly hampered by the presence of a highly tumorigenic sub-population of cancer cells called cancer stem cells (CSCs). Indeed, CSCs are resistant to chemotherapy and radiotherapy and can regenerate the tumor bulk. Hence, innovative drugs that are efficient against both
bulk tumor cells and CSCs would likely improve cancer treatment. In this study, we demonstrated that
GNS561, a new autophagy inhibitor that induces lysosomal cell death, showed significant activity against
not only the whole tumor population but also a sub-population displaying CSC features (high ALDH
activity and tumorsphere formation ability) in HCC and in liver mCRC cell lines. These results were
confirmed in vivo in HCC from a DEN-induced cirrhotic rat model in which GNS561 decreased tumor
growth and reduced the frequency of CSCs (CD90+CD45-). Thus, GNS561 offers great promise for
cancer therapy by exterminating both the tumor bulk and the CSC sub-population. Accordingly, a global
phase 1b clinical trial in liver cancers was recently completed.
#hepatocarcinoma #cancerstemcells #autophagy