Abstract A159: Dianhydrogalactitol (VAL-083) enhances activity of platinum drugs in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is treated with surgery followed by chemotherapy with either tyrosine kinase inhibitors (TKIs) or platinum-based regimens, but long term prognosis is poor. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent with proven activity against NSCLC in preclinical and clinical studies. VAL-083 is approved for the treatment of lung cancer in the Peoples Republic of China (PRC, Approval No. Guayo Zhunzi H45021133); however, clinical use has been limited by lack of mechanistic data. Here we aimed to investigate in vitro i) the role of p53 status in VAL-083 activity, ii) VAL-083 cytotoxicity in a panel of NSCLC cell lines, iii) the combination of VAL-083 with cisplatin or oxaliplatin in NSCLC cells. We further studied the combination of VAL-083 with cisplatin in NSCLC in vivo. Dependence on p53 status was investigated in isogenic HCT-116p53-/- and HCT-116p53+/+ models. VAL-083, cisplatin and oxaliplatin cytotoxicity was tested in a panel of 9 human NSCLC cell lines: 4 wt, 4 mutant and 1 null for p53. The combination potential for VAL-083 with cisplatin or oxaliplatin was investigated in 3 human NSCLC cell lines; H460 (p53wt), A549 (p53wt) and H1975 (p53mut) by determining superadditivity and synergy using the criteria of combination index (CI) Citation Format: Anne Steino, Jeffrey A. Bacha, Guanghan He, Sarath Kanekal, Nancy Dos Santos, Shun Lu, Dennis M. Brown, Zahid H. Siddik. Dianhydrogalactitol (VAL-083) enhances activity of platinum drugs in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A159.