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Publication : The drug-induced degradation of oncoproteins: an unexpected Achilles' heel of cancer cells?

First Author  Ablain J Year  2011
Journal  Cancer Discov Volume  1
Issue  2 Pages  117-27
PubMed ID  22586354 Mgi Jnum  J:185799
Mgi Id  MGI:5430238 Doi  10.1158/2159-8290.CD-11-0087
Citation  Ablain J, et al. (2011) The drug-induced degradation of oncoproteins: an unexpected Achilles' heel of cancer cells?. Cancer Discov 1(2):117-27
abstractText  Many targeted therapies against cancer are aimed at inhibiting the enzymatic activity of kinases. Thus far, this approach has undoubtedly yielded significant clinical improvements, but has only rarely achieved cures. Other drugs, which selectively elicit proteasome-dependent degradation of oncoproteins, induce the loss of cancer cell self-renewal and promote cell differentiation and/or apoptosis. In acute promyelocytic leukemia, the cooperative degradation of PML/RARA by arsenic and retinoic acid cures most patients. In this condition and others, drug-induced proteolysis of oncoproteins is feasible and underlies improved clinical outcome. Several transcription factors, nuclear receptors, or fusion proteins driving cancer growth could be candidates for proteolysis-based drug-discovery programs.
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