Source: The Sixth Affiliated Hospital
Edited by: Zheng Longfei, Wang Dongmei

Colorectal cancer is one of the most lethal malignancies in the worldwide and its incidence has shown a rapidly increasing trend in China. Even after standard clinical intervention such as surgery and chemotherapy, many patients still suffer from tumor recurrence and metastasis. Thus, drug resistance has become an important issue in treatment of colorectal cancer.

Recently, the research group directed by Prof. Xiaojian Wu and Prof. Ping Lan from the Sixth Affiliated Hospital, Sun Yat-sen University and Prof. Jing Tan from Sun Yat-sen University Cancer Center revealed a novel therapeutic strategy of PLK1 inhibitors to chemo-resistant colorectal cancer. The work entitled “Inhibition of the PLK1-coupled cell cycle machinery overcomes resistance to oxaliplatin in colorectal cancer” has been published in Advanced Science. Prof. Xiaojian Wu, Prof. Jing Tan, and Prof. Ping Lan were the corresponding authors. And Dr. Zhaoliang Yu, Dr. Peng Deng and Dr. Yufeng Chen were the co-first authors.

Previously, the research group found that PDK1-PLK1 can phosphorylate and activate MYC and regulate multiple stem cell-related genes, thus promoting the malignant transformation. Here, they further reveal that aberrant PLK1 signaling correlates with recurrence and poor prognosis of CRC patients, and higher levels of PLK1/p-PLK1 were detected in relapsed/metastatic CRC tissues than in matched primary CRC tissues, indicating PLK1 may confer resistance to oxaliplatin-based chemotherapy in CRC. The inhibition of PLK1 by genetic and pharmacological intervention significantly increased the sensitivity to oxaliplatin in vitro and in vivo. The mechanism investigation identified CDC7 as a critical downstream effector of PLK1 signaling, which was transactivated via the PLK1-MYC axis. And the targeted value of CDC7 expression was further confirmed in the in vitro and in vivo models, demonstrating the potential utility of targeting the PLK1-MYC-CDC7 axis in the treatment of oxaliplatin-based chemotherapy. Pharmacological targeting of the PLK1-MYC-CDC7 axis could enhance the efficacy of oxaliplatin, which provided potential clinical advantage in using PLK1 or CDC7 inhibitor in combination with chemotherapy regimens in treatment of CRC patients.

Link to the paper: https://doi.org/10.1002/advs.202100759