Disitamab vedotin, a novel HER2-directed antibody-drug conjugate in gastric cancer and other solid tumors

Drugs Today (Barc). 2022 Oct;58(10):491-507. doi: 10.1358/dot.2022.58.10.3408812.

Abstract

Antibody-drug conjugates (ADC), a combination of cytotoxic drugs and antibodies, have emerged as a rising star in cancer therapy. Disitamab vedotin (RC48), a novel ADC targeting human epidermal growth factor receptor 2 (HER2), is currently being explored in a variety of malignancies. Compared with conventional HER2-targeting agents, RC48 is characterized by a wider therapeutic window and less toxicity to normal tissues. In this review, we will analyze the structural elements and mechanisms of RC48. Besides, we provide a landscape on the progression of RC48 in common malignancies, focusing on RC48 in gastric or gastroesophageal junction cancer, and a brief overview of urothelial, breast and other cancers (e.g., gynecological cancer, biliary tract cancer, non-small cell lung cancer and myometrial invasive bladder cancer). Finally, we will also discuss future challenges in the development of RC48 and future directions to improve efficacy.

Keywords: Anti-HER2 agents; Antibody-drug conjugates; Disitamab vedotin; Gastric cancer; RC48; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Humans
  • Immunoconjugates* / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Receptor, ErbB-2 / metabolism
  • Stomach Neoplasms* / drug therapy

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • ERBB2 protein, human
  • Immunoconjugates
  • Receptor, ErbB-2