Journal
SCIENCE
Volume 355, Issue 6330, Pages 1163-1167Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aam7340
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Funding
- Leukemia and Lymphoma Society
- NIH [R35CA197589]
- Arvinas
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Targeted therapies for cancer are typically small molecules or monoclonal antibodies that act by inhibiting the activity of specific proteins that drive tumor growth. Although many of these drugs are effective in cancer patients, the response is often not durable because tumor cells develop resistance to the drugs. Another limitation of this strategy is that not all oncogenic driver proteins are druggable enzymes or receptors with activities that can be inhibited. Here we describe an alternative approach to targeted therapy that is based on co-opting the cellular quality-control machinery-the ubiquitin-proteasome system-to remove specific cancer-causing proteins from the cell. We first discuss examples of existing cancer drugs that work by degrading specific proteins and then review recent progress in the rational design and preclinical testing of small molecules that induce selective degradation of specific target proteins.
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