Oncogene stability and homeostasis mediated by the HSP90 chaperone is a crucial protection trait of cancer cells. Therefore, HSP90 represents an attractive therapeutic target for many cancers, including colorectal cancer. Although monotherapy has limited clinical efficacy, preclinical and early-phase clinical studies indicate improved antitumor activity when HSP90 inhibitors are combined with chemotherapies or targeted agents. This may be further improved with a biomarker-guided approach based on oncogenic HSP90 clients, or stratification based on the consensus molecular subtypes of colorectal cancer, suggesting a synergistic activity with 5-fluorouracil in preclinical models of the chemorefractory mesenchymal subtype. Furthermore, HSP90 inhibition may activate mechanisms to turn non-immunogenic tumors hot and improve their recognition by the immune system, suggesting synergy with immune checkpoint blockade.

HSP90伴侣介导的癌基因稳定性和体内稳态是癌细胞的重要保护性状。因此，HSP90代表了许多癌症（包括结直肠癌）的有吸引力的治疗靶标。尽管单一疗法的临床疗效有限，但临床前和早期临床研究表明，当HSP90抑制剂与化学疗法或靶向药物联合使用时，抗肿瘤活性会提高。这可以通过基于致癌HSP90客户的生物标志物指导方法或基于大肠癌共识分子亚型的分层来进一步改善，这表明在化学难治性间充质亚型的临床前模型中与5-氟尿嘧啶具有协同活性。此外，