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Targeting HER2 in Gastroesophageal Cancer: A New Appetite for an Old Plight.
Drugs
January 2025
Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
The incidence of gastroesophageal cancers is rising, driven, in part, by an increasing burden of risk factors of obesity and gastroesophageal reflux. Despite efforts to address these risk factors, and a growing interest in methods of population screening, the bulk of these tumours are unresectable at diagnosis. In this setting, effective systemic treatments are paramount to improve survival and quality of life.
View Article and Find Full Text PDFModular Synthesis of Anti-HER2 Dual-Drug Antibody-Drug Conjugates Demonstrating Improved Toxicity.
Bioconjug Chem
January 2025
Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112 United States.
Antibodies have gained clinical success in the last two decades for the targeted delivery of highly toxic small molecule chemotherapeutics. Yet antibody-drug conjugates (ADCs) often fail in the clinic due to the development of resistance. The delivery of two mechanistically distinct small molecule drugs on one antibody is of increasing interest to overcome these challenges with single-drug ADCs.
View Article and Find Full Text PDFDisitamab vedotin in preclinical models of HER2-positive breast and gastric cancers resistant to trastuzumab emtansine and trastuzumab deruxtecan.
Transl 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.
View Article and Find Full Text PDFThe current landscape and prospects of antibody-drug conjugates for lung cancer brain metastases: a narrative review.
Transl Lung Cancer Res
December 2024
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background And Objective: As the most common cancer to progress to brain metastases (BMs), lung cancer presents with intracranial involvement in approximately 20% of patients at the time of diagnosis and lung cancer BMs constitute approximately half of all BMs. The current clinical strategy for managing lung cancer BMs involves a combination of systemic anticancer therapies with local radiation or surgical interventions. The efficacy of systemic treatments is often constrained by the blood-brain barrier (BBB) and the poor inhibition effect of the drug itself.
View Article and Find Full Text PDF[The current treatment status and future of antibody drug conjugates in HER-2-alteration non-small cell lung cancer].
Zhonghua Zhong Liu Za Zhi
January 2025
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100021, China.
Non-small cell lung cancer(NSCLC) is one of the major histopathological types of lung cancer, accounting for about 85 percent of all lung cancers. The human epidermal growth factor receptor 2 (HER-2) alteration in NSCLC include gene mutations, gene amplifications, and protein overexpression, and is one of the important driving target. Currently, the treatment options for HER-2 altered NSCLC are still relatively limited, and more effective drugs are urgently needed.
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