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

TLDR

Drug resistance in cancer often arises from genetic changes, and in prostate cancer it has been linked to Wnt pathway activation, but detecting it via rare circulating tumor cells remains technically challenging. The study aims to enable early detection of resistance mechanisms to guide timely drug switching. They developed a non‑invasive RNA‑seq approach on single CTCs to identify resistance signatures. Miyamoto et al.

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