Drug resistance is a serious challenge in cancer treatment and cancer cells can acquire resistance through multiple mechanisms.  We have developed CXL017, which reveals selective cytotoxicity towards multi-drug resistant cancer cell lines.  Drug resistant cancer cells, HL60/MX2, also failed to acquire resistance to CXL017 and surprisingly regained sensitivity towards standard therapies.  We have investigated the mechanisms responsible for HL60/MX2 cells' resistance to standard therapies and the molecular bases for its re-sensitization upon chronic CXL017 exposure � Mcl-1 over-expression, at least partially resulted from its improved stability vie ERK1/2 activation, is a critical determinant for cross-resistance to standard therapies, while topo II� confers resistance specifically to mitoxantrone mainly via gene expression down-regulation.  Structure-activity relationship studies leading to more potent CXL candidates will also be discussed.

Anticancer drug candidate against drug resistance in leukemia and its mechanisms of action

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.