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Genes are cut and pasted into messages before they are used. Blood cancers often carry mutations in the splicing machinery, and the errors create abnormal proteins that could serve as targets or immune flags.
Spliceosome mutations (SF3B1, SRSF2, U2AF1, ZRSR2) occur in ~50% of MDS and in CLL and uveal melanoma; they cause mis-splicing, R-loops, and dependence on the remaining wild-type spliceosome (H3B-8800, negative), and on PRMT5 and NMD. Splicing produces drug-resistance isoforms (AR-V7 in prostate cancer, BCL2L1 isoforms) and neoantigens (splice-junction-derived) that may be immunogenic across patients. RNA-targeting small molecules (risdiplam-like) and antisense oligonucleotides are the therapeutic tools; MYC-driven tumours are spliceosome-dependent.
Splicing is film editing. The raw footage (pre-mRNA) is cut into a final movie. Cancer's editor makes odd cuts: some create villains (AR-V7), some create scenes no one has seen before (neoantigens), and the editing room itself becomes a place where the cancer can be attacked.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It turned a single-centre observation into a prospectively validated one and concluded that AR-V7-positive men should be offered alternatives to abiraterone and enzalutamide. It also quantified the honest limit: two assays for the same analyte disagree on nearly one sample in five.
It is the clearest evidence in prostate cancer that a blood biomarker can point to one treatment class over another, and the reason AR-V7 is discussed in guidelines despite being in no label.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
The first predictive resistance biomarker in prostate cancer, and a mechanism rather than a correlation: a receptor with no ligand-binding domain cannot be blocked by a drug that binds the ligand-binding domain. It is also the origin of the case for androgen receptor degraders, which destroy the protein rather than blocking a site the protein no longer has.
Shares Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Dana-Farber Brigham Cancer Center, Memorial Sloan Kettering Cancer Center, Acute myeloid leukaemia and the tag mechanism.
Shares Memorial Sloan Kettering Cancer Center, Melanoma, Prostate cancer and the tag mechanism.
Shares MYC, Dana-Farber Brigham Cancer Center, Chronic lymphocytic leukaemia and the tag mechanism.
Shares MYC, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares MYC, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares DNA replication stress, Dana-Farber Brigham Cancer Center and the tag mechanism.
Shares The long tail of oncogenic drivers in prostate cancer, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Dana-Farber Brigham Cancer Center, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Antigen presentation & immune editing, Memorial Sloan Kettering Cancer Center and the tag mechanism.