Language:

Therapy-Induced Senescence Drives Bone Loss

Cancer research (Chicago, Ill.), 2020-03, Vol.80 (5), p.1171-1182 [Peer Reviewed Journal]

2020 American Association for Cancer Research. ;ISSN: 0008-5472 ;EISSN: 1538-7445 ;DOI: 10.1158/0008-5472.can-19-2348 ;PMID: 31932453

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Therapy-Induced Senescence Drives Bone Loss
Author: Yao, Zhangting ; Murali, Bhavna ; Ren, Qihao ; Luo, Xianmin ; Faget, Douglas V ; Cole, Tom ; Ricci, Biancamaria ; Thotala, Dinesh ; Monahan, Joseph ; van Deursen, Jan M ; Baker, Darren ; Faccio, Roberta ; Schwarz, Julie K ; Stewart, Sheila A
Subjects: Animals ; Antineoplastic Agents - adverse effects ; Cellular Senescence - drug effects ; Disease Models, Animal ; Doxorubicin - adverse effects ; Femur - cytology ; Femur - diagnostic imaging ; Femur - pathology ; Humans ; Injections, Intraperitoneal ; Intracellular Signaling Peptides and Proteins - metabolism ; MAP Kinase Signaling System - drug effects ; Mice ; Mice, Transgenic ; Neoplasms - drug therapy ; Osteoporosis - chemically induced ; Osteoporosis - diagnosis ; Osteoporosis - pathology ; p38 Mitogen-Activated Protein Kinases - metabolism ; Paclitaxel - adverse effects ; Protein Serine-Threonine Kinases - metabolism ; X-Ray Microtomography
Is Part Of: Cancer research (Chicago, Ill.), 2020-03, Vol.80 (5), p.1171-1182
Description: 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.
Publisher: United States
Language: English
Identifier: ISSN: 0008-5472
EISSN: 1538-7445
DOI: 10.1158/0008-5472.can-19-2348
PMID: 31932453
Source: MEDLINE
Alma/SFX Local Collection

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Therapy-Induced Senescence Drives Bone Loss

2020 American Association for Cancer Research. ;ISSN: 0008-5472 ;EISSN: 1538-7445 ;DOI: 10.1158/0008-5472.can-19-2348 ;PMID: 31932453

Searching Remote Databases, Please Wait