Contemplated compositions and methods are drawn to biomarkers and methods related to treatment of neoplastic disease with Hec1 inhibitor. Gene status and/or expression levels of Hec1(HEC), Rb(RB1), and/or p53 (TP53) may be useful as biomarkers for sensitivity to treatment with a Hec1 inhibitor. In addition, Hec 1 inhibitors may show synergistic effects when used in conjunction with cytotoxic drugs.