Research ArticleCancer

Tumor-selective proteotoxicity of verteporfin inhibits colon cancer progression independently of YAP1

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Science Signaling  06 Oct 2015:
Vol. 8, Issue 397, pp. ra98
DOI: 10.1126/scisignal.aac5418

Aggregates kill cancer cells

The drug verteporfin is used clinically to enhance phototherapy and may also inhibit the transcription factor YAP1, which is often active in cancers. However, Zhang et al. found a different path to toxicity for verteporfin-mediated death of colorectal cancer cells. Verteporfin triggered the accumulation of toxic amounts of protein oligomers that selectively killed colorectal cancer cells in mice and in cells cultured under hypoxic and nutrient-deprived conditions. Normal cells in culture and in tumor-adjacent tissue sections from mice cleared these aggregates through autophagy and survived. Thus, verteporfin produces tumor-selective proteotoxicity, which may be a useful therapeutic for patients with solid tumors.

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