Editors' ChoiceCancer

Another Notch for Targeted Therapy?

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Science's STKE  12 Oct 2004:
Vol. 2004, Issue 254, pp. tw365
DOI: 10.1126/stke.2542004tw365

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that typically affects children and adolescents. Although the current cure rate is high, T-ALL patients must endure intensive regimens of highly cytotoxic chemotherapy, so there is great interest in developing targeted therapies with fewer side effects. Weng et al. now report that ~50% of T-ALLs have activating mutations in the gene encoding NOTCH1, a transmembrane receptor that regulates T cell differentiation. Together with previous evidence implicating NOTCH1 in cancer development, these results raise the possibility that inhibitors of NOTCH signaling, including the γ-secretase inhibitors, a group of drugs currently being developed for Alzheimer's disease, may merit investigation as anticancer agents.

A. P. Weng, A. A. Ferrando, W. Lee, J. P. Morris, L. B. Silverman, C. Sanchez-Irizarry, S. C. Blacklow, A. T. Look, J. C. Aster, Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306, 269-271 (2004). [Abstract] [Full Text]

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