scholarly journals Expression of the immune checkpoint molecule V-set immunoglobulin domain-containing 4 is associated with poor prognosis in patients with advanced gastric cancer

2020 ◽  
Author(s):  
So-Woon Kim ◽  
Jin Roh ◽  
Hye Seung Lee ◽  
Min-Hee Ryu ◽  
Young-Soo Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Poor Prognosis ◽  
Checkpoint Molecule ◽  
Immunoglobulin Domain

scholarly journals How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

2021 ◽  
Vol 10 (7) ◽  
pp. 1412
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Andrea Botticelli ◽  
Dario Trapani ◽  
Alessandro Parisi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Implementation ◽  
T Cell Therapy ◽  
Dismal Prognosis

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.

scholarly journals The Aberrant Expression of MicroRNA-125a-5p/IGF2BP3 Axis in Advanced Gastric Cancer and Its Clinical Relevance

2020 ◽  
Vol 19 ◽  
pp. 153303382091733
Author(s):  
Jing Zhang ◽  
Fanghui Ding ◽  
Dan Jiao ◽  
Qiaozhi Li ◽  
Hong Ma
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Advanced Gastric Cancer ◽  
Messenger Rna ◽  
Poor Prognosis ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Advanced Stage ◽  
Insulin Like Growth Factor

RNA-binding proteins have been associated with cancer development. The overexpression of a well-known RNA-binding protein, insulin-like growth factor 2 messenger RNA–binding protein 3, has been identified as an indicator of poor prognosis in patients with various types of cancer. Although gastric cancer is a relatively frequent and potentially fatal malignancy, the mechanism by which insulin-like growth factor 2 messenger RNA–binding protein 3 regulates the development of this cancer remains unclear. This study aimed to investigate the role and regulatory mechanism of insulin-like growth factor 2 messenger RNA–binding protein 3 in gastric cancer. An analysis of IGF2BP3 expression patterns reported in 4 public gastric cancer–related microarray data sets from the Gene Expression Omnibus and The Cancer Genome Atlas-Stomach Adenocarcinoma revealed strong expression of this gene in gastric cancer tissues. Insulin-like growth factor 2 messenger RNA–binding protein 3 expression in gastric cancer was further confirmed via quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively, in an in-house gastric cancer cohort (n = 30), and the association of insulin-like growth factor 2 messenger RNA–binding protein 3 expression with clinical parameters and prognosis was analyzed. Notably, stronger IGF2BP3 expression significantly correlated with poor prognosis, and significant changes in insulin-like growth factor 2 messenger RNA–binding protein 3 expression were only confirmed in patients with advanced-stage gastric cancer in an independent cohort. The effects of insulin-like growth factor 2 messenger RNA–binding protein 3 on cell proliferation were confirmed through in vitro experiments involving the HGC-27 gastric cancer cell line. MicroR-125a-5p, a candidate microRNA that target on insulin-like growth factor 2 messenger RNA–binding protein 3, decreased in advanced-stage gastric cancer. Upregulation of microR-125a-5p inhibited insulin-like growth factor 2 messenger RNA–binding protein 3, and dual-luciferase report assay indicated that microR-125a-5p inhibited the translation of IGF2BP3 by directly targeting the 3′ untranslated region. These results indicate that the microR-125a-5p/insulin-like growth factor 2 messenger RNA–binding protein 3 axis contributes to the oncogenesis of advanced gastric cancer.

scholarly journals FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer

Oncogenesis ◽  
2020 ◽  
Vol 9 (2) ◽  
Author(s):  
Takuro Hirano ◽  
Yoshinari Shinsato ◽  
Kan Tanabe ◽  
Nayuta Higa ◽  
Muhammad Kamil ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Poor Prognosis

scholarly journals Hyperprogressive disease during nivolumab or irinotecan treatment in patients with advanced gastric cancer

ESMO Open ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. e000488 ◽  
Author(s):  
Masahiko Aoki ◽  
Hirokazu Shoji ◽  
Kengo Nagashima ◽  
Hiroshi Imazeki ◽  
Takahiro Miyamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Survival Benefit ◽  
Poor Prognosis ◽  
Tumour Growth ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prior Therapy ◽  
Hyperprogressive Disease

BackgroundNivolumab showed a survival benefit for advanced gastric cancer (AGC). However, an acceleration of tumour growth during immunotherapy, (hyperprogressive disease, HPD) has been reported in various cancers. This study reviewed the HPD in patients with AGC treated with nivolumab or irinotecan.MethodsThe subjects of this retrospective study were patients with AGC with measurable lesions, and their tumour growth rates (TGR) during nivolumab or irinotecan were compared with those during prior therapy. HPD was defined as an increase in TGR more than twofold.Results34 and 66 patients received nivolumab and irinotecan in third or later line between June 2009 and September 2018 at our hospital; 22 patients receiving nivolumab had prior treatment with irinotecan, and one patient received irinotecan after nivolumab. Nivolumab and irinotecan showed no differences in disease control rates (38.2% and 34.8%) and in progression-free survival (PFS) (HR 1.1, 95% CI 0.7 to 1.6, p=0.802). The incidence of HPD was slightly higher after nivolumab (29.4%) than after irinotecan (13.5%) (p=0.0656), showing no differences in background between the patients with and without HPD. Compared between HPD and PD other than HPD after nivolumab, the HRs for PFS and overall survival (OS) were 1.1 (95% CI 0.5 to 2.7; p=0.756), and 2.1 (95% CI 0.7 to 5.8; p=0.168), but such clear difference in OS was not observed after irinotecan.ConclusionsHPD was observed more frequently after nivolumab compared with irinotecan, which was associated with a poor prognosis after nivolumab but not so clearly after irinotecan.

Chemotherapy and survival benefit in elderly patients with advanced gastric cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 45-45 ◽  
Author(s):  
Aya Sugimoto ◽  
Tsutomu Nishida ◽  
Kei Takahashi ◽  
Kaori Mukai ◽  
Tokuhiro Matsubara ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Elderly Patients ◽  
Advanced Gastric Cancer ◽  
Scoring System ◽  
Survival Benefit ◽  
Poor Prognosis ◽  
Risk Group ◽  
Univariate Analysis ◽  
Significant Difference ◽  
Total Point

45 Background:There is little evidence if chemotherapy (CT) offer survival benefit for elderly patients (EP) with advanced gastric cancer (AGC). Methods: This was a single-centre retrospective study. A total of 118 patients with AGC were hospitalized at our hospital from April 2012 to June 2016. Of them, EP older than 75 years with AGC were eligible for inclusion in the study. Basically, the treatment strategy, chemotherapy (CT) or best supportive care (BSC) were comprehensively decided according to their background. We evaluate the risk factors for survival using the Cox proportional hazard model and explored the optimal indication for CT for EP. Results: Of 118 patients with AGC, 47 patients were enrolled as EP [63% men; mean age, 81 years]. Of EP, 26 patients (55%) received CT and 21 patients received BSC. As first-line CT, 13 patients received S1 monotherapy, the others treated with combination agents. The median overall survival time (MST) was 138 days. There was no significant difference between CT and BSC group (172 vs. 118 days, p = 0. 1087). Univariate analysis revealed the following 5 factors for poor prognosis were significant (defined as p-value < 0.1): Performance status (PS) 3a 2 (HR3.7, 95% CI: 1.5-8.5), C-reactive protein levels 3a 1mg/dL (HR4.0, 95% CI: 1.8-9.4), albumin level < 3g/dL (HR2.1, 95% CI: 1.1-4.3), neutrophil/lymphocyte ratio (NLR) 3a 4 (HR3.7, 95% CI: 1.7-8.5), and diffuse type (HR1.8, 95% CI: 0.9-3.8). As each poor risk factor of 5 and age factor 3a 80 years represents point 1, we calculated total points (0-6) for each patient. Median total points of CT and BSC were 2 and 4, respectively (p = 0.0196). Therefore, we set cut-off point of 3. Then, EP with a total point of 3 and more were classified as high risk group (HR: N = 25) and the others were as low risk group (LR: N = 22). There was significantly longer MST in LR than HR (all EP; 457 vs 105 days, HR: 0.23, p = 0.0002 and EP with CT; 232 vs 113 days, HR:0.26, p = 0.0085). Conclusions: Our findings using the scoring system including 6 factors suggest that EP with a total point 3 and more, were poor prognosis and may not receive benefit from CT for AGC. When judging indication for CT in EP with AGC, this scoring system may be useful, and in case of LR (total point 0-2) may be considered an indication for CT.

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