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.
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http://dx.doi.org/10.1358/dot.2022.58.10.3408812 | DOI Listing |
Front Immunol
January 2025
Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
As an antibody-drug conjugate (ADC), disitamab vedotin (RC48) is a promising treatment targeting ERBB2 for locally advanced and metastatic bladder cancer (BLCA). However, the subtype heterogeneity of muscle-invasive bladder cancer (MIBC) often leads to different therapeutic outcomes. In our study, we aim to explore sensitivity differences and mechanisms of different molecular subtypes of MIBC to RC48 treatment and develop a strategy for combination therapy against cancer.
View Article and Find Full Text PDFTransl Oncol
January 2025
Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Laboratory of Molecular Oncology, Biomedicum, University of Helsinki, Helsinki, Finland. Electronic address:
Background: Most HER2-positive breast or gastric cancers eventually become resistant to the approved anti-HER2 antibody-drug conjugates (ADC) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). Disitamab vedotin (DV) is a novel anti-HER2 ADC that binds to a different epitope on HER2 compared to trastuzumab. We assessed the efficacy of DV in breast and gastric cancer cell lines and xenografts, including tumor models resistant to T-DM1 and T-DXd.
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January 2025
Department of Gastrointestinal Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China.
Novel therapeutic agents including disitamab vedotin (RC48, an antibody-drug conjugate) and immune-checkpoint inhibitors (e.g., PD-1 inhibitors) have provided new hope as an advanced gastric-cancer (GC) treatment.
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December 2024
Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Objective: To explore the efficacy of c in the multiline treatment of late-stage lung adenocarcinoma with Her-2 overexpression and epidermal growth factor receptor (EGFR) mutations.
Methods: We summarize the diagnosis and treatment of a female patient with EGFR 21L858R mutation combined with Her-2 overexpression in advanced lung adenocarcinoma, and analyze the effect of c in her treatment process.
Results: The patient was diagnosed with lung adenocarcinoma 8 years ago.
Ann Oncol
December 2024
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital, Beijing, China. Electronic address:
Background: Human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugates (ADCs) such as disitamab vedotin (DV) and trastuzumab deruxtecan (T-DXd) have emerged as effective treatment options and received regulatory approvals for HER2-expressing locally advanced or metastatic urothelial carcinoma (la/mUC). In addition, ADCs in combination with immunotherapy have demonstrated antitumor activity. The current study aimed to evaluate the combination of DV and toripalimab in patients with la/mUC.
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