Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15
2017; American Association for the Advancement of Science; Volume: 356; Issue: 6336 Linguagem: Inglês
10.1126/science.aal3755
ISSN1095-9203
AutoresTing Han, Maria Goralski, Nicholas Gaskill, Emanuela Capota, Jiwoong Kim, Tabitha C. Ting, Yang Xie, Noelle S. Williams, Deepak Nijhawan,
Tópico(s)Cancer-related gene regulation
ResumoAn old cancer drug's degrading new look Typically, cancer drugs that help only a small number of patients in clinical trials are not pursued. This might change in a future world of precision medicine, where biomarkers will match specific drugs to the patients most likely to respond. Han et al. identified the mechanism of action of a cancer drug called indisulam, a sulfonamide tested previously in patients with solid tumors. Indisulam and related sulfonamides killed cells by disrupting precursor mRNA splicing. The drugs targeted a specific RNA splicing factor for degradation by “gluing” it to the CUL4-DCAF15 ubiquitin ligase. Experiments with cancer cell lines suggest that future clinical trials of these drugs should focus on leukemias and lymphomas with high DCAF15 expression levels. Science , this issue p. eaal3755
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