How Prognostic and Predictive Biomarkers Are Transforming Our Understanding and Management of Advanced Gastric Cancer

Kim, Christina; Mulder, Karen; Spratlin, Jennifer L.

doi:10.1634/theoncologist.2014-0006

Cited by 19 publications

(12 citation statements)

References 140 publications

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“…Despite recent advances in the diagnosis and management of GC, patients with advanced GC have a poor prognosis and the 5-year overall survival rate remains low at ~25% due to tumor recurrence, metastasis and poor response to chemotherapy and radiotherapy (2,3). In addition, the unclear pathophysiological mechanisms of GC have limited its clinical treatment options (4). Thus, it is essential to identify the molecular characterizations of GC in order to find new diagnostic strategies and potential drugs targets.…”

Section: Introductionmentioning

confidence: 99%

miR-138 inhibits gastric cancer growth by suppressing SOX4

Pang

Zheng

et al. 2017

Oncology Reports

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MicroRNA-138 (miR-138) has been reported to be downregulated and function as a tumor suppressor in several cancers. However, the role and molecular mechanisms of miR-138 in the progression of gastric cancer (GC) remain to be clarified. The aim of the present study was to determine the role of miR-138 in GC progression. In the present study we found that miR-138 expression was downregulated in GC tissues and cell lines. Statistical analysis demonstrated that low expression levels of miR-138 were associated with advanced tumor-node-metastasis (TNM) stage, and lymph node metastasis. Function assays demonstrated that overexpression of miR-138 impaired GC cell proliferation, colony formation, migration and invasion in vitro, as well as suppressed tumor growth in vivo. Through reporter gene, qRT-PCR and western blot assays, SRY-related high mobility group box 4 (SOX4), a master mediator in epithelial-mesenchymal transition (EMT), was confirmed to be a direct target of miR-138 in GC cells. Western blot assay revealed that miR-138 overexpression inhibited EMT procession in GC cells by upregulation of epithelial marker E-cadherin and downregulation of mesenchymal markers, N-cadherin and vimentin. Furthermore, the levels of miR-138 were inversely correlated with those of SOX4 expression in GC tissues. Overexpression of SOX4 rescued the inhibition effect in GC cells caused by miR-138. Collectively, these findings indicate that miR-138 may be a potential therapeutic target for GC.

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Section: Introductionmentioning

confidence: 99%

miR-138 inhibits gastric cancer growth by suppressing SOX4

Pang

Zheng

et al. 2017

Oncology Reports

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“…In first-line treatment of HER2-positive advanced gastric cancer, the addition of trastuzumab to chemotherapy improves overall survival (7). Ramucirumab improves survival in the second-line setting of advanced gastric cancer; however, predictive biomarkers have not yet been clearly defined (30). In the present case report, the patient with chemotherapy-resistant recurrent AFPGC exhibited a significant response to ramucirumab monotherapy.…”

Section: Discussionmentioning

confidence: 62%

Significant response to ramucirumab monotherapy in chemotherapy-resistant recurrent alpha-fetoprotein-producing gastric cancer: A case report

Arakawa¹,

Tamura²,

Aiba³

et al. 2017

Oncology Letters

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Abstract. Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is a relatively rare type of gastric cancer characterized by a high incidence of liver and lymph node metastases, and a poor prognosis. Few advanced AFPGC cases treated successfully with conventional chemotherapy have been reported thus far. Although the development of molecular-targeted therapy has improved the prognosis of various types of cancer, there are currently no tailored therapies for AFPGC. In the present report, the case of a chemotherapy-resistant recurrent AFPGC patient who exhibited a significant response to ramucirumab monotherapy is presented. Following six doses of ramucirumab, a metastatic lymph node displayed central necrosis, and the patient's serum AFP levels decreased from 12,800 to 225 ng/ml. AFPGC is known to have increased vascular endothelial growth factor (VEGF) expression and rich neovascularization. Furthermore, in the present case, tumor cells were positive for VEGF. Ramucirumab is a monoclonal antibody for VEGF receptor-2 and the first anti-angiogenic drug approved for the treatment of advanced gastric cancer. However, the clinical efficacy of ramucirumab in patients with AFPGC has not been reported previously. The present report suggests that AFP production in gastric cancer can be a predictor for the response to anti-angiogenic drugs such as ramucirumab.

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“…Despite recent advances in systemic chemotherapy, an optimal global standard has not yet been established for advanced gastric cancer (2) and there is no internationally recognized standard or preferred regimen for the management of the advanced disease stage. In order to improve outcomes, it is essential to understand the molecular pathogenesis underlying gastric cancer and to identify robust prognostic or predictive biomarkers (3).…”

Section: Introductionmentioning

confidence: 99%

High expression of P21-activated kinase 5 protein is associated with poor survival in gastric cancer

et al. 2017

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Abstract. P21-activated kinase 5 (PAK5), also termed PAK7, is one of the six members of the PAK family of serine/threonine kinases, which are downstream effectors in several cancer signaling pathways. PAK5 promotes neural outgrowth, contributes to microtubule stability and induces resistance to apoptosis. However, the clinical importance of PAK5 in gastric cancer has not been comprehensively investigated. In the present study, PAK5 expression was evaluated in gastric cancer tissue samples. Furthermore, the associations between high expression of PAK5, and clinicopathological features and prognosis were examined. PAK5 expression in primary gastric cancer specimens resected from 279 patients who underwent gastrectomy at the Tokyo Medical and Dental University Hospital was evaluated using immunohistochemistry. Of the 279 patients, 44 (15.8%) exhibited high PAK5 expression, which was significantly associated with the differentiated pathological type (differentiated vs. undifferentiated; P<0.001), depth of tumor invasion (T1 vs. T2-T4; P<0.001), lymph node metastasis (N0 vs. N1-N3; P<0.001), presence of distant metastasis or recurrence (present vs. absent; P=0.038), advanced tumor stage (I vs. II-IV; P=0.001) and worse disease-specific survival (P=0.013). In stage I-III disease, 38/254 (15.0%) patients exhibited high PAK5 expression, and high expression of PAK5 was significantly associated with relapse-free interval (P=0.044). PAK5 may serve an important role in tumor progression and influence the outcome of patients with gastric cancer.

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How Prognostic and Predictive Biomarkers Are Transforming Our Understanding and Management of Advanced Gastric Cancer

Cited by 19 publications

References 140 publications

miR-138 inhibits gastric cancer growth by suppressing SOX4

miR-138 inhibits gastric cancer growth by suppressing SOX4

Significant response to ramucirumab monotherapy in chemotherapy-resistant recurrent alpha-fetoprotein-producing gastric cancer: A case report

High expression of P21-activated kinase 5 protein is associated with poor survival in gastric cancer

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