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Most cancers have the wrong number of chromosomes; normal cells do not. If that difference creates a specific weakness, a drug against it would spare normal tissue by definition.
This open question asks whether aneuploidy itself is a druggable vulnerability: most cancers have the wrong number of chromosomes and normal cells do not, so a drug against that difference would spare normal tissue. CIN cells depend on KIF18A, the spindle checkpoint, BCL-XL and proteostasis, and KIF18A inhibitors (sovilnesib, AMG 650) showed activity in platinum-resistant Ovarian cancer in 2024-25. The hypothesis is that a CIN score selects patients whose tumours regress on KIF18A or spindle-checkpoint therapy, and that STING modulators (cGAS-STING pathway) add immunity. The test is a randomised phase 2 of a KIF18A inhibitor against chemotherapy in CIN-high, TP53-mutant ovarian cancer; see also Whole-genome doubling (WGD).
One idea 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.
This paper is the reason TP53 status, MDM2 amplification and CDKN2A loss are read together in tumour genomes. It frames the current drug development around MDM2 inhibitors and mutant p53 reactivators as attempts to restore a network rather than a single protein.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, Memorial Sloan Kettering Cancer Center, TP53, Ovarian cancer and the tags mechanism, open-question.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, The Francis Crick Institute, TP53 and the tags mechanism, open-question.
Shares Stanford Health Care / Stanford Cancer Institute, Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center, Ovarian cancer, Triple-negative breast cancer (TNBC) and the tags mechanism, open-question.
Shares Chromosomal instability & aneuploidy, Stanford Health Care / Stanford Cancer Institute and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center, Triple-negative breast cancer (TNBC) and the tags mechanism, open-question.
Shares Stanford Health Care / Stanford Cancer Institute and the tags mechanism, open-question.
Shares Memorial Sloan Kettering Cancer Center and the tags mechanism, open-question.