Editors' ChoiceCancer

A degrading game plan for cancer therapy

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Sci. Signal.  23 Jun 2015:
Vol. 8, Issue 382, pp. ec173
DOI: 10.1126/scisignal.aac8280

Certain classes of proteins that contribute to cancer development are challenging to target therapeutically. Winter et al. devised a chemical strategy that, in principle, permits the selective degradation of any protein of interest. The strategy involves chemically attaching a ligand known to bind the desired protein to another molecule that hijacks an enzyme that directs proteins to the cell's protein degradation machinery. In a proof-of-concept study, they demonstrated selective degradation of a transcriptional coactivator called bromodomain-containing protein 4 and delayed the progression of leukemia in mice.

G. E. Winter, D. L. Buckley, J. Paulk, J. M. Roberts, A. Souza, S. Dhe-Paganon, J. E. Bradner, Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348, 1376–1381 (2015). [Abstract] [Full Text]