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Review
. 2022 Oct 21;23(20):12659.
doi: 10.3390/ijms232012659.

Her-2 Targeted Therapy in Advanced Urothelial Cancer: From Monoclonal Antibodies to Antibody-Drug Conjugates

Víctor Albarrán  1 , Diana Isabel Rosero  1 , Jesús Chamorro  1 , Javier Pozas  1 , María San Román  1 , Ana María Barrill  1 , Víctor Alía  1 , Pilar Sotoca  1 , Patricia Guerrero  1 , Juan Carlos Calvo  1 , Inmaculada Orejana  1 , Patricia Pérez de Aguado  1 , Pablo Gajate  1
Affiliations
Review

Her-2 Targeted Therapy in Advanced Urothelial Cancer: From Monoclonal Antibodies to Antibody-Drug Conjugates

Víctor Albarrán et al. Int J Mol Sci. .

Abstract

Metastatic urothelial cancer, associated with a poor prognosis, is still major cause of cancer-related death, with scarce options of effective treatment after progression to platinum-based chemotherapy and immunotherapy. The human epithelial growth factor receptor 2 (Her-2) has been identified as a new therapeutic target in medical oncology. However, despite the encouraging results in breast and gastric cancers, clinical trials with anti-Her-2 monoclonal antibodies and tyrosine-kinase inhibitors have shown limited efficacy of this strategy in urothelial tumors. Notably, more favorable data have been recently shown that antibody-drug conjugates are currently emerging as a novel promising approach for Her-2 targeted therapy in advanced urothelial cancer.

Keywords: Her-2; antibody-drug conjugate; monoclonal antibody; targeted therapy; tyrosine-kinase inhibitor; urothelial cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Main downstream oncogenic pathways unleashed by Her-2 activation. Unlike other receptors from ERBB family, Her-2 does not have an extracellular ligand and its heterodimerization is promoted by the ligand-binding of the other three receptors (HER1/EGFR, HER3, HER4). Its activation unleashes the phosphorylation of intracytoplasmic tyrosine substrates and the initiation of downstream transduction pathways with pro-oncogenic effects.
See this image and copyright information in PMC

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