Abstract 987: XCE853: A novel anticancer candidate preferentially killing drug-resistant human tumor cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (8_Supplement), p.987-987
• Main Authors: Gutmann, Matthieu, Briand, Jean-François, Prevost, Gregoire Pierre, Carniato, Denis, Pitty, Marc-Henry
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-987

Cancer drug pan-resistance is associated with patients having a disease progression despite receiving new treatments. Often resistance arises in two steps, initially, the tumor responds to the drug, but not all tumor cells are killed leading to a selection of tumor cells that do not respond to any current drug. The nature of the residual disease is linked to different conditions such the efflux pumps, the quiescent cells, the stem cells, the DNA repair deficiency or the EMT. Here, we have identified a family of synthetic compounds displaying a preferential antiproliferative activity on drug resistant human cancer cells. The lead compound XCE853 is 5 to 94 more potent on drug resistant cancer cell lines compared to their parental tumor cell lines (HL60/HL60-Doxorubicin; MCF7/MCF7-Doxorubicin; A2780/A2780-Cisplatin and A549/AA549-Taxotere). XCE853 induced a strong and irreversible cytolysis of MCF7-Adriamycin cells after a short exposure in vitro (250nM, 6 hours). The mechanism of action of XCE853 is independent of efflux pumps and involves an early high ROS production leading to cell death by autophagy. The antitumor activity of XCE853 is also observed using in vivo xenograft models of human NSCLC. Altogether, these data support further efforts on this drug candidate to better understand its molecular mechanism of action and the description of the most sensitive tumor types. Citation Format: Matthieu Gutmann, Jean-François Briand, Gregoire Pierre Prevost, Denis Carniato, Marc-Henry Pitty. XCE853: A novel anticancer candidate preferentially killing drug-resistant human tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 987. doi:10.1158/1538-7445.AM2013-987