Insights into next developments in advanced gastric cancer

Purpose of review: The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations. Recent findings: A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing. Summary: Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: GASTROINTESTINAL TRACT: Edited by Alain Hendlisz Source Type: research

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SummaryAlthough several large clinical trials have been conducted in order to investigate targeted inhibition of several molecular pathways in gastric cancer, only a  limited number of targeted therapies have been introduced in clinical routine. Besides scientific interest, international guidelines recommend investigation of some distinct molecular alterations, which are associated with therapeutic consequences. These are (i) human epidermal growth factor rece ptor 2 (HER2), (ii) programmed death receptor 1 (PD-L1) and (iii) microsatellite instability (MSI). There are some emerging markers, such as Epst...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
Contributors : Ryosuke Matsukane ; Mitsuhiro HayashiSeries Type : Expression profiling by arrayOrganism : Homo sapiensOur novel drug imaging technique revealed that trastuzumab, which is representative antibody drug for breast and gastric cancer in clinical, distributed heterogeneously inside tumor even though its target receptor, HER2 (Human epidermal growth factor receptor 2) expressed homogeneously. For identifying a predominant regulator of trastuzumab tumor delivery in the tumor site, we tried tumor region-specific microarray analysis according to trastuzumab distribution in patient derived xenograft model.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
Conclusion: Temporal pharmacological modulation of membrane HER2 may be clinically relevant and exploitable for pretargeted molecular imaging and therapy in gastric tumors.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Source Type: research
Conclusion: This study suggests that the prevalence of GC cases overexpressing the HER2 oncogene in Costa Rica is less than 8%. This is the first attempt ever undertaken to estimate the prevalence of HER2-positivity in GC in Costa Rica. PMID: 31645889 [PubMed]
Source: Ecancermedicalscience - Category: Cancer & Oncology Tags: Ecancermedicalscience Source Type: research
AbstractABP 980 was developed as a biosimilar to trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), that is indicated for the treatment of HER2-positive metastatic breast cancer, early breast cancer (EBC), and metastatic gastric cancer. ABP 980 is approved in the United States, European Union, and Japan for all the indications of trastuzumab, based on the totality of evidence (TOE) gathered by the systematic step-wise accumulation of comparative analytical, preclinical, and clinical (pharmacokinetics [PK], efficacy, safety and immunogenicity) data for ABP  980 and trastuzumab...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsResults from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer in Japanese patients.
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
ConclusionOur111In-anti-CDH17 Mab D2101 depicted CDH17-positive gastric cancer xenografts in vivo and has the potential to be an imaging probe for the diagnosis of primary lesions and lymph-node metastasis in gastric cancer.
Source: Annals of Nuclear Medicine - Category: Nuclear Medicine Source Type: research
AbstractThe systemic treatment options for advanced gastric cancer (GC) have evolved rapidly in recent years. We have reviewed the recent data of clinical trial incorporating targeted agents, including inhibitors of angiogenesis, human epidermal growth factor receptor 2 (HER2), mesenchymal –epithelial transition, epidermal growth factor receptor, mammalian target of rapamycin, claudin-18.2, programmed death-1 and DNA. Addition of trastuzumab to platinum-based chemotherapy has become standard of care as front-line therapy in advanced GC overexpressing HER2. In the second-line setting , ramucirumab with paclitaxel sign...
Source: Experimental Hematology and Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundIncidence of gastric cancer (GC) shows different distribution in Italy, with higher incidence in the north and center. We retrospectively analyzed the clinical data of patients resected at the Hospital of Cremona between January 2007 and December 2016. Available clinical variables were linked with survival to identify possible prognostic factors.Materials and methodsVariables analyzed were age, sex, type of surgery, site, histology, invasion, nodal status, resection margins, grade, HER2 status,Helicobacter pylori infection (neo)adjuvant chemotherapy, adjuvant chemoradiotherapy, neutrophil-to-lymphocyte ra...
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsGC patients who exhibited markers that can serve as an indication for known targeted therapy represent 40.4% of cases. The IT group was associated with a better prognosis. No benefit with standard adjuvant treatment appears to be achieved in MSI/PD-L1+ GCs.
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research
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