RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance

Author:

Miyamoto David T.12,Zheng Yu13,Wittner Ben S.14,Lee Richard J.14,Zhu Huili1,Broderick Katherine T.1,Desai Rushil1,Fox Douglas B.1,Brannigan Brian W.1,Trautwein Julie1,Arora Kshitij S.15,Desai Niyati15,Dahl Douglas M.16,Sequist Lecia V.14,Smith Matthew R.14,Kapur Ravi7,Wu Chin-Lee15,Shioda Toshi1,Ramaswamy Sridhar14,Ting David T.14,Toner Mehmet7,Maheswaran Shyamala18,Haber Daniel A.134

Affiliation:

1. Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

2. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

3. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

4. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

5. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

6. Department of Urology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

7. Center for Bioengineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

8. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

Abstract

Circulating signals of drug resistance 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 non-invasive 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 it is used in clinical practice. Science , this issue p. 1351 ; see also p. 1283

Funder

NIH

Department of Defense

Howard Hughes Medical Institute

National Cancer Institute

NCI

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

Burroughs Wellcome Fund

Prostate Cancer Foundation

Johnson & Johnson

Massachusetts General Hospital

Stand Up to Cancer

Charles Evans Foundation

Federal Share Program and Income

Affymetrix, Inc.

Mazzone Program–Dana-Farber Harvard Cancer Center

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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