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In hormone-positive breast cancer, oestrogen binds its receptor, which switches on genes that make the cell divide. Every endocrine therapy cuts this chain somewhere.
Aromatase converts androgens to oestradiol (in ovaries pre-menopause, fat and tumour post-menopause). Oestradiol binds ERα (ESR1), which dimerises, recruits co-activators, and drives transcription of cyclin D1, MYC, PGR, and growth factors, activating CDK4/6 and cross-talking with PI3K and HER2. Tamoxifen (SERM) competes; aromatase inhibitors deplete ligand; fulvestrant and oral SERDs degrade ER; vepdegestrant (PROTAC) degrades it via cereblon. Resistance: ESR1 ligand-binding-domain mutations (ligand-independent, ~30% after AI), cyclin D1/CDK4 amplification, PI3K activation, lineage switch.
A key (oestrogen) turns a lock (ER) that opens a gate to the division machinery. Aromatase inhibitors stop making keys, tamoxifen jams a fake key in the lock, SERDs and PROTACs remove the lock from the door, and ESR1 mutations are a lock that opens without any key.
Shares Abemaciclib, Palbociclib, Estrogen receptor (ERα), PIK3CA / PI3K-alpha.
Shares Vepdegestrant, Ribociclib, CDK4/6 inhibitors, PROTACs & molecular glues (targeted protein degradation).
Shares Elacestrant, Ribociclib, Letrozole (and other aromatase inhibitors), Abemaciclib.
Shares Vepdegestrant, Abemaciclib, CDK4/6 inhibitors, PROTACs & molecular glues (targeted protein degradation).
Shares Vepdegestrant, Palbociclib, CDK4/6 inhibitors, PROTACs & molecular glues (targeted protein degradation).
Shares Abemaciclib, CDK4/6, Estrogen receptor (ERα), CDK4/6 inhibitors.
Shares Ribociclib, Letrozole (and other aromatase inhibitors), CDK4/6, Estrogen receptor (ERα).
Shares Ribociclib, Abemaciclib, Palbociclib, CDK4/6 inhibitors.