Combination therapies with HSP90 inhibitors against colorectal cancer

Publication date: Available online 30 January 2019Source: Biochimica et Biophysica Acta (BBA) - Reviews on CancerAuthor(s): Kushtrim Kryeziu, Jarle Bruun, Tormod K. Guren, Anita Sveen, Ragnhild A. LotheAbstractOncogene 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.
Source: Biochimica et Biophysica Acta (BBA) Reviews on Cancer - Category: Cancer & Oncology Source Type: research