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Antibody drugs need their target to still be present. After one fails, checking which surface markers remain would guide the choice of the next one instead of guessing.
Antigen loss and downregulation are documented mechanisms of ADC, bispecific and CAR-T failure. A standardised multiplex panel measuring the main clinical antigens (HER2, TROP2, HER3, CEACAM5, B7-H3, Nectin-4, FOLR1 and others) on a progression biopsy, or by immuno-PET where available, would let clinicians select the next agent by present antigen rather than by tumour type convention.
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.
This study confirmed HER2 as a prognostic marker and a therapeutic target, showed that immunohistochemistry could identify the patients, and extended the target to ovarian cancer. It set up the clinical development of trastuzumab and the HER2 testing that every breast cancer now receives.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, Payload-class switching as the rule for ADC sequencing, B7-H3, TROP2.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER3, TROP2.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, Payload-class switching as the rule for ADC sequencing, TROP2, Acquired resistance to every therapy.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, B7-H3, HER2.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2.
Shares Payload-class switching as the rule for ADC sequencing, Acquired resistance to every therapy, Histopathology & immunohistochemistry, Antibody-drug conjugate (ADC).
Shares B7-H3, TROP2, HER2, Antibody-drug conjugate (ADC).
Shares HER3, Single-cell & spatial profiling, Acquired resistance to every therapy.