Colorectal cancer is the third most common cancer in the world, with an annual incidence of 2 million cases. The success of first-line chemotherapy plays a crucial role in determining the disease outcome. Therefore, there is an increasing demand for precision medicine to predict drug responses and optimize chemotherapy in order to increase patient survival and reduce the related side effects. Patient-derived organoids have become a popular in vitro screening model for drug-response prediction for precision medicine. However, there is no established correlation between oxaliplatin and drug-response prediction. Here, we suggest that organoid culture conditions can increase resistance to oxaliplatin during drug screening, and we developed a modified medium condition to address this issue. Notably, while previous studies have shown that survivin is a mechanism for drug resistance, our study observed consistent survivin expression irrespective of the culture conditions and oxaliplatin treatment. However, clusterin induced apoptosis inhibition and cell survival, demonstrating a significant correlation with drug resistance. This study’s findings are expected to contribute to increasing the accuracy of drug-response prediction in patient-derived APC mutant colorectal cancer organoids, thereby providing reliable precision medicine and improving patient survival rates.
结直肠癌是全球第三大常见癌症，年发病数达200万例。一线化疗的成功与否对疾病预后起着决定性作用。因此，精准医疗在预测药物反应和优化化疗方案方面的需求日益增长，以期提高患者生存率并减少相关副作用。患者来源类器官已成为精准医疗中药物反应预测的重要体外筛选模型。然而，目前尚未建立奥沙利铂与药物反应预测之间的明确关联。本研究提出类器官培养条件可能增强药物筛选过程中对奥沙利铂的耐药性，并开发了改良培养基条件以解决该问题。值得注意的是，虽然既往研究表明存活蛋白是耐药机制之一，但本研究发现无论培养条件与奥沙利铂处理如何变化，存活蛋白表达均保持稳定。而簇集蛋白通过抑制细胞凋亡促进细胞存活，显示出与耐药性的显著相关性。本研究结果有望提高APC突变型结直肠癌患者来源类器官的药物反应预测准确性，从而为精准医疗提供可靠依据，提升患者生存率。
肿瘤(癌症)患者之家