结直肠癌（colorectal cancer, CRC）是世界第三大恶性肿瘤，其中约30% CRC 患者存在KRAS突变激活。KRAS野生型患者可从当前临床抗EGFR靶向药物治疗中获益，而KRAS突变患者不能获益。由于没有合适的靶向药物，KRAS突变激活的CRC患者治疗预后更差。因此KRAS突变激活的靶向治疗已成为目前CRC治疗亟待解决的关键问题之一。我们的前期研究发现下调PEAK1能在体内、外水平上显著抑制KRAS突变激活CRC细胞的增殖和侵袭转移，提示其可作为KRAS突变激活CRC的潜在治疗靶点。本研究拟解析PEAK1在CRC发生和发展过程中的作用，阐明其在CRC中过度活化的原因及下游调控分子机制，并系统评价其靶向治疗KRAS突变型CRC的效果及可行性，以期突破当前KRAS突变激活CRC无特异靶标药物的困局，为KRAS突变激活CRC的临床治疗提供新的具有重大潜力的作用靶点和治疗策略。

Colorectal cancer (CRC) is the third most common cancer worldwide. Approximately 30% of CRC patients carry KRAS mutations, which are well established biomarkers for predicting the poor efficacy of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in CRC chemotherapy. Thus, for the CRCs with KRAS mutations, it is urgent to explore the new drug targets and therapies. Our recent studies indicated that knockdown of PEAK1 can inhibit the growth and metastasis of KRAS-dependent CRC cells in vitro and in vivo, which suggested that PEAK1 can be a potential treatment target for KRAS-dependent CRCs. Therefore, based on above, in this study we aim to study the effects of PEAK1 on proliferation, migration and invasion of KRAS-dependent CRC cells, investigate its up- and downstream signaling and then evaluate the feasibility of treating KRAS-dependent CRCs by targeting PEAK1. This study could break the current predicament of no targeted drugs for KRAS-dependent CRCs and provide them a new approach.