Advances in the Management of HER2-positive Advanced Gastric and Gastroesophageal Junction Cancer

Bang, Yung‐Jue

doi:10.1097/mcg.0b013e3182557307

Cited by 73 publications

(47 citation statements)

References 61 publications

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“…ERBB2 is a member of the epidermal growth factor receptor family, which has previously been associated with the enhanced proliferation rates of tumor cells (38). In addition, previous studies have demonstrated that ERBB2 is a target gene of miR-375 (20), that the PI3K/Akt signal pathway is associated with ERBB2 regulation, and that the activation of the ERBB2/PI3K/Akt pathway may promote resistance of cancer cells to drugs (26).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of microRNA-375 increases the cisplatin-sensitivity of human gastric cancer cells by regulating ERBB2

Zhou

et al. 2015

Experimental and Therapeutic Medicine

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Abstract.Resistance to chemotherapy is a major challenge in the effective treatment of patients with gastric cancer; however, the mechanisms underlying chemoresistance in gastric cancer cells are yet to be elucidated. MicroRNAs (miRNAs) have previously been associated with cancer progression and sensitivity to chemotherapy; therefore, the present study aimed to identify miRNAs that may influence the sensitivity of human gastric cancer cells to cisplatin (DDP) treatment. Initially, miRNAs that were differentially expressed between the DDP-sensitive SGC7901 human gastric cancer cell line and DDP-resistant SGC7901/DDP cell line were identified using high-throughput sequencing technology. miRNA-375 (miR-375), which was shown to be downregulated in the SGC7901/DDP cells, has previously been associated with numerous types of cancer; however, to the best of our knowledge, a role for miR-375 in the DDP-sensitivity of gastric cancer cells has yet to be explored. In the present study, the expression levels of miR-375 were significantly downregulated in the SGC7901/DDP cells, as compared with the SGC7901 cells, as demonstrated by reverse transcription-quantitative polymerase chain reaction. In addition, upregulation of miR-375 significantly enhanced the anti-proliferative and apoptosis-inducing effects of DDP, whereas downregulation of miR-375 decreased these effects. Subsequently, western blot analysis demonstrated that upregulation of miR-375 in the SGC7901/DDP cells increased their sensitivity to DDP treatment via regulating the protein expression levels of erb-b2 receptor tyrosine kinase 2 and phosphorylated-Akt. The results of the present study indicate that the expression levels of miR-375 may influence the sensitivity of human gastric cancer cells to the effects of DDP; thus suggesting that a combination of miR-375 regulation and DDP may be considered a novel strategy in the treatment of patients with chemoresistant gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Upregulation of microRNA-375 increases the cisplatin-sensitivity of human gastric cancer cells by regulating ERBB2

Zhou

et al. 2015

Experimental and Therapeutic Medicine

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“…[77][78][79] It is expressed in normal epithelial cells, and amplification and/or overexpression of this gene has been reported in up to 30% of breast cancers 80 and in 9% to 27% of patients with gastric cancer. Overexpression of HER2/neu is slightly greater at the esophagogastric junction in comparison to the stomach 81,82 and overexpression in the stomach varies with histologic type (intestinal-type greater than diffuse type) and differentiation (moderately differentiated greater than poorly differentiated). 83 ERBB2 (HER2/neu) appears to be an important prognostic factor in gastric cancer, but the literature is conflicting, as not all studies have shown an association between HER2/neu overexpression and poor prognosis.…”

Section: Mek Genementioning

confidence: 99%

Select Biomarkers for Tumors of the Gastrointestinal Tract: Present and Future

Bartley

Hamilton

2014

Archives of Pathology &Amp; Laboratory Medicine

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Context Advances in molecular biomarkers of the gastrointestinal tract have contributed to a decline in the incidence of and mortality from diseases of the gastrointestinal tract. The discovery and clinical validation of new biomarkers are important to personalized cancer therapy, and numerous clinical trials are currently ongoing to help identify individualized therapy affecting these biomarkers and molecular mechanisms they represent. Distinct molecular pathways leading to cancers of the colorectum, esophagus, stomach, small bowel, and pancreas have been identified. Using biomarkers in these pathways to direct patient care, including selection of proper molecular testing for identification of actionable mutations and reporting the results of these biomarkers to guide clinicians and genetic counselors, is paramount. Objective To examine and review select clinically actionable biomarkers of the colon, esophagus, stomach, small bowel, and pancreas, including present and future biomarkers with relevant clinical trials. Data Sources Extensive literature review and practical and consultation experience of the authors. Conclusions Although numerous biomarkers have been identified and are currently guiding patient therapy, few have shown evidence of clinical utility in the management of patients with gastrointestinal cancers. Inconsistent results and discordant proposed algorithms for testing were identified throughout the literature; however, the potential for biomarkers to improve outcomes for patients with gastrointestinal cancer remains high. Continued advances through high-quality studies are needed.

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“…In ToGA trial, a combination of chemotherapy and trastuzumab demonstrated a significant OS benefit in metastatic gastric cancer patients. [15] Its value as a prognostic factor of HER2 in gastric cancer is controversial and may vary based on whether the patient receives chemotherapy. For instance, Terashima et al [16] investigated the HER2 status in gastric cancer and found that HER2 was not a prognostic marker in the ing HER2 with antibody caused significant changes in the radiosensitivity of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Pretreatment HER2 Status in Gastric Cancer Patients Treated with Postoperative Chemoradiotherapy

Güler¹

2017

TJ Oncol

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OBJECTIVEOur purpose was to evaluate the prognostic or predictive importance of HER2 status in gastric cancer patients treated with postoperative chemoradiotherapy. METHODSWe retrospectively analyzed the records of 49 gastric cancer patients treated with curative intent between April 2012 and January 2017; we also assessed the impact of HER2 status on prognosis and treatment outcomes. RESULTSDuring a median follow-up period of 14.6 months (range, 4.0-56.97 months), two patients (4%) had local recurrence and 21 patients (43%) developed distant metastasis. We found no statistically significant difference in metastasis frequency rates between HER2 negative (−) and positive (+) patients. The median overall survival (OS) and disease-free survival (DFS) for the whole group were 24.9 and 24.2 months, respectively. Although there was no significant difference in OS and DFS according to HER2 status, there was a negative trend in OS (p=0.451) and DFS (p=0.633) in HER2 (+) patients. CONCLUSIONAlthough our study did not demonstrate any statistically significant importance of HER2 status in gastric cancer patients treated with postoperative chemoradiotherapy, the median OS of 13 months in HER2 (+) patients and 24.9 months for HER2 (−) patients warranted randomized trials with larger cohorts.

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Advances in the Management of HER2-positive Advanced Gastric and Gastroesophageal Junction Cancer

Cited by 73 publications

References 61 publications

Upregulation of microRNA-375 increases the cisplatin-sensitivity of human gastric cancer cells by regulating ERBB2

Upregulation of microRNA-375 increases the cisplatin-sensitivity of human gastric cancer cells by regulating ERBB2

Select Biomarkers for Tumors of the Gastrointestinal Tract: Present and Future

Prognostic Value of Pretreatment HER2 Status in Gastric Cancer Patients Treated with Postoperative Chemoradiotherapy

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