Targeted and novel therapy in advanced gastric cancer

Selim, Julie H.; Shaheen, Shagufta; Sheu, Wei-Chun; Hsueh, Chung-Tsen

doi:10.1186/s40164-019-0149-6

Cited by 63 publications

(57 citation statements)

References 148 publications

(150 reference statements)

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“…The primary goal of molecular profiling and subclassification of GC/GEJC into subtypes is to facilitate the optimal selection of patients in whom molecular targeted therapies can achieve optimum results [6]. HER2 positivity or amplification has been identified in at least a quarter of patients with GC/GEJC [10]. Therapeutic approaches to target HER2 in HER2-positive GC/GEJC include anti-HER2 monoclonal antibodies and HER2-targeting TKIs.…”

Section: Discussionmentioning

confidence: 99%

“…Varlitinib, also recognized as ASLAN001 and ARRY-334543, is a reversible small-molecule TKI of the EGFR family [10].…”

Section: Varlitinibmentioning

confidence: 99%

“…Neratinib, also recognized as HKI-272, is a reversible small-molecule TKI of the EGFR family [10]. A preclinical study showed that neratinib exhibited therapeutic benefits in HER2-positive GC cells [9].…”

Section: Neratinibmentioning

confidence: 99%

“…HER2 does not bind to specific ligands, and it is activated through hetero-or homo-dimerization with the other EGFR members, leading to aberrant activation of important oncogenic signaling pathways, such as phosphatidylinositol three-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) [8,9]. HER2 positivity can be established through immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH), and it is seen in at least more than 15% of patients with GC/GEJC [10,11]. At the clinical level, HER2 expression is correlated with poor clinicopathological prognostic outcomes, such as old age, advanced-stage disease, large tumor size, high tumor grade, lymphovascular space invasion, and poor survival rates [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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The Use of Epidermal Growth Factor Receptor Type 2-Targeting Tyrosine Kinase Inhibitors in the Management of Epidermal Growth Factor Receptor Type 2-Positive Gastric Cancer: A Narrative Review

AlMazmomy

Al-Hayani

Alomari

et al. 2019

Cureus

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Gastric cancer (GC), including gastroesophageal junction cancer (GEJC), continues to be one of the most frequently diagnosed neoplasms globally. Moreover, GC/GEJC is a principal cause of neoplasm-related fatalities. Early-stage GC/GEJC has a favorable five-year overall survival (OS) rate with surgical resection. However, the vast majority of patients present with advanced inoperable or metastatic disease with a very unfavorable five-year OS rate. Such patients are left with very limited therapeutic options, such as systemic chemotherapy, targeted therapy, and immunotherapy, all of which can be performed as monotherapy or in various combinations. The molecular profiling of GC has revealed several personalized therapeutic vulnerabilities, one of which is the expression of epidermal growth factor receptor type 2 (EGFR2, also known as HER2). HER2 overexpression or amplification is present in a fair subset of patients with GC/GEJC and has been shown to correlate with poor clinicopathological prognostic outcomes. Generally, treatment schemes to tackle HER2 in HER2-positive GC/GEJC comprise the use of anti-HER2 monoclonal antibodies or HER2-targeting tyrosine kinase inhibitors (TKIs). In this study, we engage in a narrative review of the available phase II and III literature on the efficacy and safety of HER2-targeting TKIs in the management of HER2positive GC/GEJC.

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Section: Discussionmentioning

confidence: 99%

“…Varlitinib, also recognized as ASLAN001 and ARRY-334543, is a reversible small-molecule TKI of the EGFR family [10].…”

Section: Varlitinibmentioning

confidence: 99%

Section: Neratinibmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Use of Epidermal Growth Factor Receptor Type 2-Targeting Tyrosine Kinase Inhibitors in the Management of Epidermal Growth Factor Receptor Type 2-Positive Gastric Cancer: A Narrative Review

AlMazmomy

Al-Hayani

Alomari

et al. 2019

Cureus

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“…GC is an important leading cause of cancer-associated death worldwide, with an estimated 1,000,000 new cases and approximately 700,000 deaths every year derived from the cancer statistics of 2018 [1]. Despite the advances in the diagnosis and treatment of GC, the prognosis for patients with GC remains poor due to most of the diagnosis during its middle to late stages [2,3].…”

Section: Introductionmentioning

confidence: 99%

Systematic Construction and Validation of an RNA Binding Proteins-Based Signature for Prognostic Prediction in Gastric Cancer

Zhang

Wang

et al. 2020

Preprint

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Background: Gastric cancer (GC) is one of the most common cancers with high incidence and mortality worldwide. Recently, RNA-binding proteins (RBPs) have drawn more and more attention for its role in cancer pathophysiology. In this study, we aim to explore the function and clinical implication of RBPs in GC. Methods: RNA sequencing data along with the corresponding clinical information of GC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed RNA-binding proteins (DERBPs) between tumor and normal tissues were identified by ‘limma’ package. Functional enrichment analysis and the protein-protein interaction (PPI) network were harnessed to explore the function and interaction of DERBPs. Next, Univariate and multiple Cox regression were applied to screen prognosis-related hub RBPs and to construct a signature for BC. Meanwhile, a nomogram was built based on the same RBPs. Results: A total of 296 DERBPs were found, and most of them mainly related to post-transcriptional regulation of RNA and ribonucleoprotein. A PPI network of DERBPs was constructed, consisting of 262 nodes and 2567 edges. A prognostic signature was built depended on seven prognosis-related hub RBPs that could divide GC patients into high- and low-risk groups. Survival analysis showed that the high-risk group had a worse prognosis compared to the low-risk group and the time-dependent receiver operating characteristic (ROC) curves suggested that the signature existed moderate predictive capacities of survival for GC patients. Similar results were obtained from another independent set GSE84437, confirming the robustness of signature. Calibration plots reported good consistency between overall survival (OS) prediction by nomogram and actual observation. Conclusion: The findings of this study would provide evidence of the effect of RBPs on GC as well as offering novel potential biomarkers in prognosis prediction and clinical decision for GC patients.

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Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges

et al. 2021

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Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular, and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low-risk factors and hereditary GC is caused by inherited high-risk mutations, so far identified only for the diffuse histotype.DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC-specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC-related histological subtypes (Signet-Ring Cell Carcinoma (SRCC) and Poorly Cohesive Carcinoma not otherwise specified (PCC-NOS)). Indeed, DGC and DGC-related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC-NOS vs SRCC.In this systematic review, we revised the histological presentations, molecular classifications, and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC-NOS). We aimed at identifying histology-associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC-NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC-specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.

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Targeted and novel therapy in advanced gastric cancer

Cited by 63 publications

References 148 publications

The Use of Epidermal Growth Factor Receptor Type 2-Targeting Tyrosine Kinase Inhibitors in the Management of Epidermal Growth Factor Receptor Type 2-Positive Gastric Cancer: A Narrative Review

The Use of Epidermal Growth Factor Receptor Type 2-Targeting Tyrosine Kinase Inhibitors in the Management of Epidermal Growth Factor Receptor Type 2-Positive Gastric Cancer: A Narrative Review

Systematic Construction and Validation of an RNA Binding Proteins-Based Signature for Prognostic Prediction in Gastric Cancer

Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges

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