☆ 4.6 Review

Research Progress of Antibody-Drug Conjugate Therapy for Advanced Gastric Cancer

FRONTIERS IN ONCOLOGY (2022)

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Summary: Recent years have seen a shift in cancer treatment towards therapies tailored to specific molecular aberrations and immunologic markers, rather than solely relying on histology. Several histology-agnostic therapies are now adopted in clinical practice for treating patients, and novel antibody-drug conjugates (ADCs) have shown promise in treating solid tumors. The multihistological expansion of ADCs poses both challenges and opportunities for cancer treatment.

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From AVATAR Mice to Patients: RC48-ADC Exerted Promising Efficacy in Advanced Gastric Cancer With HER2 Expression

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Summary: RC48-ADC demonstrated significant antiproliferative effects on gastric cancer cells, especially in HER2-positive cells, both in vitro and in vivo. In clinical practice, it showed satisfactory efficacy in HER2-positive and HER2 moderately expressed GC patients, and promising efficacy in HER2-positive patients who have progressed after anti-HER2 therapy.

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Summary: Despite new treatment options, the long-term prognosis of recurrent or inoperable gastric cancer remains poor. Antibody-drug conjugates (ADCs) have shown promising results in clinical trials. Novel HER2-ADCs have led to breakthrough results for HER2(+) gastric cancer, but there are still questions that need to be addressed, especially in clinical settings. Translational research to elucidate ADCs' mechanisms of action or resistance will lead to more sophisticated use of ADCs and combination strategies.

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Current treatment and recent progress in gastric cancer

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Summary: Gastric cancer is a common cause of cancer death worldwide, with treatment options including systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy. Classification and biomarkers for gastric cancer help in personalized therapy and identifying populations most likely to benefit from immunotherapy and targeted therapy.

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Trastuzumab deruxtecan for the treatment of HER2-positive advanced gastric cancer: a clinical perspective

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The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

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Joshua Z. Drago et al.

Summary: Nine ADCs are currently approved for cancer treatment, with many more in development. Advances in synthetic biochemistry have led to a new generation of ADCs promising improved tissue specificity and cytotoxicity. Despite impressive activity against treatment-refractory cancers, challenges such as systemic toxicity and acquired resistance remain. This review discusses the design, mechanism of action, and limitations of ADCs, proposing strategies to maximize their therapeutic benefit for cancer patients.

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Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors

Yingying Xu et al.

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Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand?

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Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer

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EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors

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