HER-2 positive gastric cancer: Current targeted treatments

Gastric cancer (GC) is highly metastatic and characterized by HER2 amplification. Aberrant HER2 expression drives metastasis, therapy resistance, and tumor recurrence. HER2 amplification contributes to drug resistance by upregulating DNA repair enzymes and drug afflux proteins, reducing drug efficac...

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Bibliographic Details
Published in:International journal of biological macromolecules 2024-08, Vol.274 (Pt 1), p.133247, Article 133247
Main Authors: Malla, Rama Rao, Nellipudi, Haasita Reddy, Srilatha, Mundla, Nagaraju, Ganji Purnachandra
Format: Article
Language:English
Subjects:
Adjunct therapies
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Drug Resistance, Neoplasm - drug effects
Gastric cancer
Gene Expression Regulation, Neoplastic - drug effects
Humans
Metastasis
Molecular Targeted Therapy
Receptor, ErbB-2 - antagonists & inhibitors
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
Resistance
Signal Transduction - drug effects
Signaling
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Trastuzumab - pharmacology
Trastuzumab - therapeutic use
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Summary:Gastric cancer (GC) is highly metastatic and characterized by HER2 amplification. Aberrant HER2 expression drives metastasis, therapy resistance, and tumor recurrence. HER2 amplification contributes to drug resistance by upregulating DNA repair enzymes and drug afflux proteins, reducing drug efficacy. HER2 modulates transcription factors critical for cancer stem cell properties, further impacting drug resistance. HER2 activity is influenced by HER-family ligands, promoting oncogenic signaling. These features point to HER2 as a targetable driver in GC. This review outlines recent advances in HER2-mediated mechanisms and their upstream and downstream signaling pathways in GC. Additionally, it discusses preclinical research investigation that comprehends trastuzumab-sensitizing phytochemicals, chemotherapeutics, and nanoparticles as adjunct therapies. These developments hold promise for improving outcomes and enhancing the management of HER2-positive GC. •Identified HER2-mediated molecular mechanisms in advanced gastric cancer.•Explored downstream signaling of HER2 in advanced gastric cancer.•Reviewed upstream regulators of HER2 in advanced gastric cancer.•Discussed strategies for targeting advanced gastric cancer.
ISSN:0141-8130
1879-0003
1879-0003
DOI:10.1016/j.ijbiomac.2024.133247