Preclinical Activity Of The Rational Combination Of Apatinib In Combination With Cpt-11 In Kras-Mutant Colorectal Cancer Patient-Derived Xenograft Model

Colorectal cancer (CRC) is a leading cause of cancer deaths. Despite the introduction of targeted therapies in clinical practice for CRC, the overall outcome of CRC is not satisfactory, owing to tumor recurrence and distant metastasis. Treatment of metastasis CRC patients with KRAS mutation with anti-angiogenic drugs, has been shown to bring significant advances and represents standard of care. However, drug resistance ultimately develops and new treatment strategies are urgently required. The Patient-derived xenograft (PDX) model is an important drug evaluation animal model research tool for more personalized precision medicine. In this study, one KRAS-mutant CRC PDX model was established. We investigated antitumor response of a novel selective VEGFR2 inhibitor apatinib alone or in combination with CPT-11 in the CRC PDX model. Our study using PDX model of KRAS-mutant CRC showed that combination treatment significantly inhibited the growth of tumors, reduced micro vessel density, suppressed proliferation, and increased apoptosis. Taken together, these preclinical data may suggest a rational combination strategy with apatinib and CPT-11 for patients with KRAS mutant CRC.