| First Author | Yao Z | Year | 2020 |
| Journal | Cancer Res | Volume | 80 |
| Issue | 5 | Pages | 1171-1182 |
| PubMed ID | 31932453 | Mgi Jnum | J:285805 |
| Mgi Id | MGI:6393239 | Doi | 10.1158/0008-5472.CAN-19-2348 |
| Citation | Yao Z, et al. (2020) Therapy-Induced Senescence Drives Bone Loss. Cancer Res 80(5):1171-1182 |
| abstractText | Chemotherapy is important for cancer treatment, however, toxicities limit its use. While great strides have been made to ameliorate the acute toxicities induced by chemotherapy, long-term comorbidities including bone loss remain a significant problem. Chemotherapy-driven estrogen loss is postulated to drive bone loss, but significant data suggests the existence of an estrogen-independent mechanism of bone loss. Using clinically relevant mouse models, we showed that senescence and its senescence-associated secretory phenotype (SASP) contribute to chemotherapy-induced bone loss that can be rescued by depleting senescent cells. Chemotherapy-induced SASP could be limited by targeting the p38MAPK-MK2 pathway, which resulted in preservation of bone integrity in chemotherapy-treated mice. These results transform our understanding of chemotherapy-induced bone loss by identifying senescent cells as major drivers of bone loss and the p38MAPK-MK2 axis as a putative therapeutic target that can preserve bone and improve a cancer survivor's quality of life. SIGNIFICANCE: Senescence drives chemotherapy-induced bone loss that is rescued by p38MAPK or MK2 inhibitors. These findings may lead to treatments for therapy-induced bone loss, significantly increasing quality of life for cancer survivors. |
