Human Epidermal Growth Factor Receptor-2 Gastric Adenocarcinoma: Expanding Therapy of a Recognized Target

Article Genetics & Heredity

Five hub genes contributing to the oncogenesis and trastuzumab-resistance in gastric cancer

Fahai Chen et al.

Summary: This study identified key genes related to trastuzumab resistance and gastric cancer progression through integrated analysis of different databases, providing valuable information for the diagnosis and treatment of gastric cancer.

GENE (2023)

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Article Oncology

Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial

Kensei Yamaguchi et al.

Summary: This study aimed to investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-low gastric or gastroesophageal junction adenocarcinoma. The results showed that T-DXd has clinical activity in heavily pretreated patients with HER2-low gastric/GEJ adenocarcinoma.

JOURNAL OF CLINICAL ONCOLOGY (2023)

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Article Oncology

Zanidatamab + chemotherapy as first-line treatment for HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA).

Elena Elimova et al.

JOURNAL OF CLINICAL ONCOLOGY (2023)

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Article Oncology

Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial

Josep Tabernero et al.

Summary: This study aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer. The results showed increased overall survival and progression-free survival, higher objective response rate, and comparable safety in the pertuzumab arm.

GASTRIC CANCER (2023)

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Article Oncology

Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02) : primary and updated analyses from a single-arm, phase 2

Eric Van Cutsem et al.

Summary: The DESTINY-Gastric02 trial is a phase 2 study evaluating the efficacy of trastuzumab deruxtecan in HER2-positive advanced gastric and gastro-oesophageal junction cancer. The results demonstrate clinically meaningful response rates, supporting its use as second-line therapy for these patients.

LANCET ONCOLOGY (2023)

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Article Oncology

Research progress of antibody-drug conjugates therapy for HER2-low expressing gastric cancer

Minghui Yu et al.

Summary: Gastric cancer is a highly fatal malignant tumor for which systemic treatment, particularly targeting the Human epidermal growth factor receptor 2 (HER2), is the primary approach. Antibody-drug conjugates (ADCs), novel humanized anti-HER2 monoclonal antibodies, and tyrosine kinase inhibitors (TKIs) have emerged as promising options for the treatment of HER2 expressing as well as low-expressing gastric cancer. This article reviews several promising ADC drugs and related trials for the treatment of HER2 low-expression gastric cancer.

TRANSLATIONAL ONCOLOGY (2023)

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Review Oncology

Antibody-drug conjugates: the clinical development in gastric cancer

Yingze Zhu et al.

Summary: Gastric cancer is one of the most common malignant tumors worldwide, but the efficacy of conventional treatments is limited. Antibody-drug conjugates (ADCs) have emerged as a promising approach for selective targeting of cancer cells. Clinical studies have shown promising results and significant progress in ADC-based therapies for gastric cancer. Currently, several ADCs targeting different receptors are being investigated in clinical trials for gastric cancer patients.

FRONTIERS IN ONCOLOGY (2023)

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Meeting Abstract Oncology

MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+gastric or gastroesophageal junction adenocarcinoma-Trial in progress

Daniel V. T. Catenacci et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Review Oncology

Novel ADCs and Strategies to Overcome Resistance to Anti-HER2 ADCs

Elena Diaz-Rodriguez et al.

Summary: A proportion of breast tumors carry the oncogenic HER2 protein, and while therapies targeting HER2 have shown efficacy, resistance remains a significant clinical issue. The emergence of antibody-drug conjugates (ADCs) has provided a new category of antitumor agents for HER2+ breast tumors. With two FDA-approved anti-HER2 ADCs in clinical use and others in development, there is hope for improving outcomes and overcoming resistance in HER2-positive breast cancer patients.

CANCERS (2022)

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Review Oncology

Resistance mechanisms to HER2-targeted therapy in gastroesophageal adenocarcinoma: A systematic review

Dionne Blange et al.

Summary: This study systematically investigated the resistance mechanisms to HER2-targeted therapy in gastric and esophageal adenocarcinoma. It was found that resistance mechanisms include changes in the HER2 receptor, upregulation of compensatory receptors, and activation of multiple signaling pathways. Clinical research is needed to overcome these resistance mechanisms.

CANCER TREATMENT REVIEWS (2022)

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Article Medicine, General & Internal

Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

Shanu Modi et al.

Summary: Trastuzumab deruxtecan demonstrated significantly longer progression-free and overall survival compared to physician's choice chemotherapy in patients with HER2-low metastatic breast cancer.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Review Oncology

HER2 Inhibition in Gastric Cancer-Novel Therapeutic Approaches for an Established Target

Caroline Fong et al.

Summary: This paper summarizes the evidence supporting HER2 targeting in stomach cancers, reviews mechanisms of drug resistance, and outlines new treatment approaches that may change the way we treat this disease.

CANCERS (2022)

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Article Cell Biology

Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma

Yang Zhang et al.

Summary: This clinical trial evaluates the efficacy and tolerability of ARX788 in patients with HER2-positive advanced gastric adenocarcinoma. The results demonstrate that ARX788 has promising anti-tumor activity and good tolerability in these patients.

CELL REPORTS MEDICINE (2022)

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Article Oncology

HERIZON-GEA-01: Zanidatamab plus chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma

Josep Tabernero et al.

Summary: This study aims to evaluate and compare the efficacy and safety of zanidatamab plus chemotherapy with or without tislelizumab to the standard of care as first-line treatment for advanced/metastatic HER2-positive gastroesophageal adenocarcinoma.

FUTURE ONCOLOGY (2022)

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Article Oncology

Margetuximab with retifanlimab as first-line therapy in HER2D/PD-L1D unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A

D. V. T. Catenacci et al.

Summary: This study evaluated a novel treatment regimen, the combination of margetuximab and retifanlimab, in patients with HER2-positive metastatic gastric and gastroesophageal adenocarcinoma. The results showed that this regimen had a favorable toxicity profile and achieved a high objective response rate. However, the study was discontinued early due to recent advances in the treatment of this type of cancer.

ESMO OPEN (2022)

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Meeting Abstract Oncology

Preliminary results from a phase I study using the bispecific, human epidermal growth factor 2 (HER2)-targeting antibody-drug conjugate (ADC) zanidatamab zovodotin (ZW49) in solid cancers

K. Jhaveri et al.

ANNALS OF ONCOLOGY (2022)

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Review Oncology

MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma

Daniel V. T. Catenacci et al.

Summary: This study describes the design and rationale of a clinical trial evaluating the use of margetuximab plus retifanlimab or margetuximab plus tebotelimab in unresectable metastatic/locally advanced gastric/gastroesophageal junction adenocarcinoma as first-line therapy. Primary endpoints include objective response rate, overall survival, and safety/tolerability.

FUTURE ONCOLOGY (2021)

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Meeting Abstract Oncology

Zanidatamab (ZW25) in HER2-expressing gastroesophageal adenocarcinoma (GEA): Results from a phase I study.

Funda Meric-Bernstam et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Multidisciplinary Sciences

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

Yelena Y. Janjigian et al.

Summary: The study results demonstrate that adding pembrolizumab to trastuzumab and chemotherapy significantly reduces tumor size, induces complete responses in some patients, and improves objective response rate in HER2-positive gastric or gastro-oesophageal junction adenocarcinoma.

NATURE (2021)

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Article Oncology

Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase II study

Zhi Peng et al.

Summary: The study reported the efficacy and safety of a novel anti-HER2 antibody RC48 in patients with HER2-overexpressing gastric cancer, showing promising therapeutic activity and manageable safety, suggesting potential application in patients who have previously received at least two lines of chemotherapy.

CANCER COMMUNICATIONS (2021)

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Meeting Abstract Oncology