Abstract
High-throughput sequencing and functional characterization of the cancer transcriptome have uncovered cancer-specific dysregulation of RNA splicing across a variety of cancers. Alterations in the cancer genome and dysregulation of RNA splicing factors lead to missplicing, splicing alteration-dependent gene expression and, in some cases, generation of novel splicing-derived proteins. Here, we review recent advances in our understanding of aberrant splicing in cancer pathogenesis and present strategies to harness cancer-specific aberrant splicing for therapeutic intent.
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Acknowledgements
R.F.S. was supported, in part, by MSK-ICTTP T32-CA009207 and an American Society of Hematology Research Training Award for Fellows. O.A.-W. is supported by the Leukemia & Lymphoma Society, NIH R01s CA251138, HL128239 and CA242020, NIH/NCI 1P50 254838-01 and the Edward P. Evans MDS Foundation.
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O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine, Inc., Merck, Prelude Therapeutics and Janssen and is on the Scientific Advisory Board of Envisagenics, Inc., AIChemy, Harmonic Discovery, Inc., and Pfizer Boulder. O.A.-W. has received prior research funding from H3B Biomedicine, Nurix Therapeutics and LOXO Oncology unrelated to the current manuscript. The remaining authors declare no competing interests.
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Stanley, R.F., Abdel-Wahab, O. Dysregulation and therapeutic targeting of RNA splicing in cancer. Nat Cancer 3, 536–546 (2022). https://doi.org/10.1038/s43018-022-00384-z
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DOI: https://doi.org/10.1038/s43018-022-00384-z
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