Editors' ChoiceCancer

Circulating signals of drug resistance

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Sci. Signal.  22 Sep 2015:
Vol. 8, Issue 395, pp. ec273
DOI: 10.1126/scisignal.aad4801

Cancer drugs often lose their effectiveness because tumors acquire genetic changes that confer drug resistance. Ideally, patients would be switched to a different drug before tumor growth resumes, but this requires early knowledge of how resistance arose. Miyamoto et al. have developed a noninvasive method to spot resistance by sequencing RNA transcripts in single circulating tumor cells (CTCs) (see the Perspective by Nanus and Giannakakou). For example, in prostate cancer patients, drug resistance was triggered by activation of the Wnt signaling pathway. But CTCs are rare and fragile, and the technology needs further development before use in clinical practice.

D. T. Miyamoto, Y. Zheng, B. S. Wittner, R. J. Lee, H. Zhu, K. T. Broderick, R. Desai, D. B. Fox, B. W. Brannigan, J. Trautwein, K. S. Arora, N. Desai, D. M. Dahl, L. V. Sequist, M. R. Smith, R. Kapur, C.-L. Wu, T. Shioda, S. Ramaswamy, D. T. Ting, M. Toner, S. Maheswaran, D. A. Haber, RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349, 1351–1356 (2015). [Abstract] [Full Text]

D. M. Nanus, P. Giannakakou, Cancer therapies that are gone with the Wnt. Science 349, 1283–1284 (2015). [Summary] [Full Text]