Journal
NATURE MEDICINE
Volume 23, Issue 4, Pages 461-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4291
Keywords
-
Funding
- Koch Institute Frontier Research Program through Michael and Inara Erdei Fund
- Kathy and Curt Marble Cancer Research Fund
- Koch Institute from National Cancer Institute [P30-CA14051]
- National Cancer Institute [CA034992]
- Integrative Cancer Biology Program [U54-CA112967-09]
- Center of Cancer Research
- Intramural Program of the National Cancer Institute, NIH [Z01 BC006150-19]
- National Institute of General Medical Sciences [T32GM007753]
- Misrock Postdoctoral Fellowship
Ask authors/readers for more resources
Cisplatin and its platinum analogs, carboplatin and oxaliplatin, are some of the most widely used cancer chemotherapeutics. Although cisplatin and carboplatin are used primarily in germ cell, breast and lung malignancies, oxaliplatin is instead used almost exclusively to treat colorectal and other gastrointestinal cancers. Here we utilize a unique, multi-platform genetic approach to study the mechanism of action of these clinically established platinum anti-cancer agents, as well as more recently developed cisplatin analogs. We show that oxaliplatin, unlike cisplatin and carboplatin, does not kill cells through the DNA-damage response. Rather, oxaliplatin kills cells by inducing ribosome biogenesis stress. This difference in drug mechanism explains the distinct clinical implementation of oxaliplatin relative to cisplatin, and it might enable mechanistically informed selection of distinct platinum drugs for distinct malignancies. These data highlight the functional diversity of core components of front-line cancer therapy and the potential benefits of applying a mechanism-based rationale to the use of our current arsenal of anti-cancer drugs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available