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The classic account of the HER family of receptors, explaining why HER2 is such a powerful cancer driver: it is the preferred partner for the other three receptors and turns their signals up, which is what trastuzumab and later HER2 drugs exploit.
Yarden and Sliwkowski described the four ErbB receptors (EGFR, HER2, HER3 and HER4) as a layered signalling network in which ligands select receptor pairs, the pairs determine which intracellular pathways are engaged, and the network's outputs control proliferation, survival and differentiation. They emphasised that HER2 has no ligand of its own but is the preferred dimerisation partner, that HER3 lacks kinase activity but couples strongly to PI3K, and that HER2 overexpression or EGFR mutation deregulates the whole network, which explains the activity of antibodies and kinase inhibitors against these receptors.
This review is the conceptual basis for trastuzumab, pertuzumab, HER2 antibody-drug conjugates and EGFR inhibitors, and for the HER3-mediated resistance that later drugs try to overcome.
Shares Slamon 1987: HER2 gene amplification marks an aggressive form of breast cancer, Deliver CAR-T cells straight into the fluid around the brain, Re-map the tumour's surface proteins before choosing the next antibody drug, Use the brain's own transport door to carry antibody drugs across.
Shares HER3, Receptor tyrosine kinase activation, EGFR, HER2.
Shares Alpha radioligands after ADC failure, Dual-payload ADCs in first line to prevent resistance, Re-map the tumour's surface proteins before choosing the next antibody drug.
Shares Slamon 1987: HER2 gene amplification marks an aggressive form of breast cancer, Roche / Genentech, HER2.
Shares HER4 (ERBB4), EGFR, HER2.
Shares HER3, Receptor tyrosine kinase activation, HER2.
Shares Alpha radioligands after ADC failure, Deliver CAR-T cells straight into the fluid around the brain, Re-map the tumour's surface proteins before choosing the next antibody drug.