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Although KMT2C has been established as a tumour suppressor, the precise molecular mechanisms by which its deficiency drives metastasis and therapy resistance remain incompletely understood. This review comprehensively examines the multifaceted roles of KMT2C in breast cancer pathogenesis, with a particular emphasis on its interplay with critical oncogenic signalling networks and functional axes, including the IFN\u03b3\u2010EMT\/MET axis, the MAPK\/ERK and RAS\/PI3K\/AKT\/mTOR pathways, and the KDM6A\u2013MMP3 regulatory circuit. Furthermore, we discuss emerging therapeutic strategies for KMT2C\u2010deficient breast cancers, such as epigenetic modulators (EZH2 inhibitors, KDM6A inhibitors, and BET inhibitors), DNA damage response (DDR)\u2010targeting agents, and pathway\u2010specific inhibitors. These insights not only elucidate the complex biological functions of KMT2C in breast cancer but also provide a rationale for developing precision therapies tailored to KMT2C\u2010mutant tumours.<\/jats:p>","DOI":"10.1002\/ctm2.70617","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T06:43:17Z","timestamp":1770878597000},"source":"Crossref","is-referenced-by-count":1,"title":["Targeting lysine methyltransferase 2C deficiency: New frontiers in breast cancer therapy and prognosis"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5103-6586","authenticated-orcid":false,"given":"Shuangmei","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of 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