Combination therapies with HSP90 inhibitors against colorectal cancer |
| |
Authors: | Kushtrim Kryeziu Jarle Bruun Tormod K Guren Anita Sveen Ragnhild A Lothe |
| |
Institution: | 1. Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway;2. K.G. Jebsen Colorectal Cancer Research Centre, Division for Cancer Medicine, Oslo University Hospital, Norway;3. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;4. Department of Oncology, Oslo University Hospital, Oslo, Norway |
| |
Abstract: | 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. |
| |
Keywords: | Corresponding author at: Department of Molecular Oncology Institute for Cancer Research Oslo University Hospital P O Box 4953 Nydalen 0424 Oslo Norway HSP90 Colorectal cancer Combination therapy Molecular stratification Biomarker |
本文献已被 ScienceDirect 等数据库收录! |
|