Ganetespib synergizes with cyclophosphamide to improve survival of mice with autochthonous tumors in a mutant p53-dependent manner.

ABSTRACT: The DNA-alkylating cytotoxic agent cyclophosphamide (CTX) is commonly used in the clinic to treat hematological malignancies like lymphomas and leukemias as well as solid tumors, but shows dose-dependent potentially life-threatening toxicities and can induce secondary malignancies. Thus, the clinical utility of CTX would be improved if a companion drug could be identified that allows lowering the CTX dose, while maintaining or even increasing its antineoplastic therapeutic efficacy. In mouse models, high-dose CTX (300 mg/kg) is effective in treating T-lymphomas, while low dose (defined here as 100 mg/kg) is ineffective. We previously showed that the HSP90 inhibitor ganetespib potently suppresses T-lymphoma initiation and progression and extends overall survival (OS) in hotspot knockin mice

SUBMITTER: Alexandrova EM 

PROVIDER: S-EPMC5386516 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature