MORC2增加三阴性乳腺癌对PARP1抑制剂敏感性的研究

PARP1 inhibitors have been entered clinical trials, targeted the treatment of triple negative breast cancer (TNBC). How to improve the efficacy of PARP1 inhibitors in TNBC is currently one of the key scientific issues needed to be resolved. MORC2 is a new protein involved in chromatin remodeling, of which molecular mechanism in cancer targeted therapy is still unknown. Our recently preliminary data showed that MORC2 interacted with PARP1 in vivo,but the impact of this interaction on PARP1inhibitor is unclear. In the present study, we aimed to address the functional role as well as molecular mechanism for PARP1 activity and the sensitivity of PARP1 inhibitors using a variety of model systems and technologies. The expected findings from this study will reveal new target for increasing the sensitivity of PARP1 inhibitors in the therapy of TNBC. Collectively, in the light of the solid research background and preliminary data, we strongly believe that this study is definitely feasible, novel, and innovative and has the potential clinical translation implications.

PARP1抑制剂是已进入临床试验、靶向治疗三阴性乳腺癌（TNBC）的化疗药物。如何提高PARP1抑制剂在TNBC中的疗效是目前急需解决的关键科学问题之一。MORC2是一个参与染色体重塑的分子，其在肿瘤靶向治疗中的作用及其分子机制目前知之甚少。我们前期预实验结果显示，MORC2与PARP1在体内相互结合，但其相互作用对PARP1抑制剂的活性是否产生影响目前尚不清楚。本项目拟在此基础上，采用多种模型和技术，系统深入的阐释MORC2、PARP1相互结合后对PARP1活性及其抑制剂敏感性影响的分子机制。本研究的预期成果将为提高PARP1抑制剂在治疗TNBC中的敏感性提供新的探索途径。本课题具有扎实的研究背景和基础，具有可行性、创新性和重要的临床转化应用价值。