How to overcome chemotherapy resistance has always been a hot and difficult problem in the field of tumor research. Wu Xiaojian's research group of the Sixth Affiliated Hospital of Sun Yat-sen University and Tan Jing's research group of the Center for Cancer Prevention and Control of Sun Yat-sen University used omics sequencing data to integrate and excavate PLK1, a potentially relevant target of colorectal cancer chemotherapy resistance, and conducted drug trial verification on the model of tumor sources in multiple patients, systematically exploring the treatment mechanism of PLK1 inhibitors in colorectal cancer. The results of the study found that the combined use of PLK1 inhibitors can significantly improve the anti-tumor effect of oxaliplatin, which provides new treatment ideas for patients with bowel cancer who are resistant to chemotherapy drugs or have tumor recurrence. The research paper was recently published in the journal Advanced; Science.
Clinically, a considerable number of patients have tumor recurrence and metastasis due to chemotherapy resistance after radical treatment of bowel cancer. In order to explore potential therapeutic targets to overcome chemotherapy resistance, the research team first conducted an integrated analysis of the gene chip data of 54 colorectal cancer tumor tissues and paired paracancerous mucosal tissues, and found that the PLK1 signaling pathway was overactivated, suggesting that PLK1 may be an effective therapeutic target for colorectal cancer.
In addition, the research team conducted a prognostic analysis of the cohort of 343 colorectal cancer patients, collected paired samples of 27 colorectal cancer patients before chemotherapy and after tumor recurrence, and found that patients with high expression of PLK1 and p-PLK1 had higher tumor recurrence rates, suggesting that they may be associated with chemotherapy resistance to tumors. At the same time, PLK1 inhibitors can significantly enhance the inhibitory effect of oxaliplatin on tumor cells, which has been verified in colorectal cancer cell lines, organoid models of patient tumor origin, and PDX models.
The research team explored the therapeutic potential of PLK1 inhibitors in colorectal cancer, elucidated the pharmacological mechanism of the combination of PLK1 inhibitors and oxaliplatin, and proposed a therapeutic strategy that targeted inhibition of PLK1-MYC-CDC7 signaling pathways can effectively improve the sensitivity of oxaliplatin, which provides new treatment ideas for patients with bowel cancer who are chemotherapy resistant or have tumor recurrence.
[Reporter] Jiang Ling
[Correspondent] Dai Xi'an Yu illuminated