scholarly journals Treatment Strategies of Gastric Cancer—Molecular Targets for Anti-angiogenic Therapy: a State-of-the-art Review

2021 ◽  
Author(s):  
Magdalena Tyczyńska ◽  
Paweł Kędzierawski ◽  
Kaja Karakuła ◽  
Jacek Januszewski ◽  
Krzysztof Kozak ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Strategies ◽  
Molecular Targets ◽  
Final Analysis ◽  
Vast Number ◽  
Angiogenic Therapy ◽  
Angiogenic Inhibitor ◽  
Angiogenesis Process ◽  
Gastric Cancer Treatment ◽  
Gastric Cancer Patients

Abstract Purpose Recent studies have suggested that molecular targets for the anti-angiogenic therapy might constitute a basis for additional therapy in gastric cancer treatment. A vast number of molecules, receptors, pathways, specific interactions, and thus strategies that target gastric cancer angiogenesis specifically have been reported in numerous research articles and clinical trials. Methods We conducted a systematic literature review of molecularly targeted treatment strategies in gastric cancer on the following databases—PubMed, Google Scholar, and Scopus—on September 20, 2020. Multiple articles and evaluations were searched for studies reporting newly found and promising molecular anti-angiogenic therapy pathways. Eventually, 39 articles regarding the anti-angiogenic therapy in gastric cancer were included in the final analysis. Results As a consequence of the release of the pro-angiogenic molecules from the tumour cells, gastric cancer presents high angiogenic capability. Therefore, potential schemes for future treatment strategies include the decrease of the process ligands as well as the expression of their receptors. Moreover, the increase in the angiogenic inhibitor levels and direct aim for the inner walls of the endothelial cells appear as a promising therapeutic strategy. Beyond that, angiogenesis process inhibition seems to indirectly exaggerate the effects of chemotherapy in the considered patients. Conclusions The anti-angiogenic treatment in gastric cancer patients evaluates its significance especially in the early stages of the malignancy. The studies conducted so far show that most of the meaningful angiogenic factors and receptors with the potential molecular pathways should be further evaluated since they could potentially play a substantial role in future therapies.

scholarly journals Underestimated Value of Sarcopenia in Gastric Cancer Surgery

2020 ◽  
Vol 19 (1-2) ◽  
pp. 12-19
Author(s):  
Martynas Lukšta ◽  
Raminta Lukšaitė-Lukštė ◽  
Augustinas Baušys ◽  
Kęstutis Strupas
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Bioelectrical Impedance ◽  
Significant Risk Factor ◽  
Impedance Analysis ◽  
Routine Clinical Practice ◽  
Gastric Cancer Treatment

Surgery remains the only potentially curative option for gastric cancer, although it is related to high postoperative morbidity and mortality rate. Approximately every second gastric cancer patient is diagnosed with sarcopenia, which is a significant risk factor for postoperative complications and poor long-term outcomes. However, sarcopenia is underestimated in routine clinical practice, since it remains the interest of clinical trials. Sarcopenia diagnostic criteria are not fully standardized, but it consists of tests for muscle strength, quantity and quality. They include grip strength, chair stand test, computed tomography, magnetic resonance imaging, ultrasound, bioelectrical impedance analysis and densitometry tests. Regarding the growing evidence for sarcopenia impact on surgical gastric cancer treatment results, it is a high probability that sarcopenia assessment will come to routine clinical practice. Although, until then there is a need for further clinical trials to standardize the diagnostic and to find effective treatment strategies.

scholarly journals Application of Data Mining for the Prediction of Mortality and Occurrence of Complications for Gastric Cancer Patients

Entropy ◽  
2019 ◽  
Vol 21 (12) ◽  
pp. 1163 ◽  
Author(s):  
Cristiana Neto ◽  
Maria Brito ◽  
Vítor Lopes ◽  
Hugo Peixoto ◽  
António Abelha ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Data Mining ◽  
Cancer Patients ◽  
Healthcare Delivery ◽  
Treatment Strategies ◽  
Data Mining Algorithms ◽  
Prediction Of Mortality ◽  
Hospital Stays ◽  
Gastric Cancer Patients ◽  
Mining Algorithms

The development of malign cells that can grow in any part of the stomach, known as gastric cancer, is one of the most common causes of death worldwide. In order to increase the survival rate in patients with this condition, it is essential to improve the decision-making process leading to a better and more efficient selection of treatment strategies. Nowadays, with the large amount of information present in hospital institutions, it is possible to use data mining algorithms to improve the healthcare delivery. Thus, this study, using the CRISP methodology, aims to predict not only the mortality associated with this disease, but also the occurrence of any complication following surgery. A set of classification models were tested and compared in order to improve the prediction accuracy. The study showed that, on one hand, the J48 algorithm using oversampling is the best technique to predict the mortality in gastric cancer patients, with an accuracy of approximately 74%. On the other hand, the rain forest algorithm using oversampling presents the best results when predicting the possible occurrence of complications among gastric cancer patients after their in-hospital stays, with an accuracy of approximately 83%.

VIKTORY trial: Report on AZD1775/paclitaxel in TP53 mutation (+) GC, selumetinib/paclitaxel in ras aberrant GC, AZD5363/paclitaxel in PIK3CA mt and biomarker negative, savolitinib/docetaxel in met (+), and vistusertib/paclitaxel in RICTOR(+) GC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4024-4024 ◽  
Author(s):  
Jeeyun Lee ◽  
Seung Tae Kim ◽  
Peter G. Mortimer ◽  
Simon J Hollingsworth ◽  
Elizabeth A. Harrington ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tp53 Mutation ◽  
Molecular Targets ◽  
Predictive Biomarker ◽  
Metastatic Gastric Cancer ◽  
Molecular Signatures ◽  
Molecular Screening ◽  
Study Protocols ◽  
Gastric Cancer Patients ◽  
Clinical Trial Information

4024 Background: The VIKTORY trial is a biomarker-based umbrella trial in GC. Methods: See table below. Results: From June 2014 to Jan 2017, 432 metastatic gastric cancer patients were enrolled. 124 (28.7%) were treated on one of the associated study protocols. At January 2017, 25 pts were allocated to selumetinib/paclitaxel arm, 25 to AZD1775/paclitaxel arm, 16 to AZD5363/paclitaxel arm, 16 to vistusertib/paclitaxel arm, 4 to savolitinib monotherapy, 19 to savolitinib/docetaxel arm, 19 to phase I AZD6738/paclitaxel arm. Initial efficacy signals have been seen in several arms (selumetinib/paclitaxel, 6 of 21 evaluable patients in PR). Correlative analyses between molecular signatures and treatment response are ongoing and will be presented at the meeting. For vistusertib/paclitaxel in the biomarker negative arm, we found RICTOR amplification as a promising predictive biomarker for response. Two (of three) GC patients with RICTOR amplification achieved PR to vistusertib/paclitaxel. Conclusions: This is one of the first attempts to undertake a biomarker-driven trial in metastatic GC. 28.7% of the patients were guided to one of the parallel arms based on molecular screening outcomes. We were able to identify potential molecular targets in the biomarker-negative arm, for further assessment in new protocols. Clinical trial information: 02299648. [Table: see text]

Treatment outcomes of peritoneal carcinomatosis arising from gastric cancer with no measurable disease using systemic chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14558-e14558
Author(s):  
Guk Jin Lee ◽  
Sook Hee Hong ◽  
Sang Young Roh ◽  
Young Seon Hong ◽  
Kyo Young Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Peritoneal Carcinomatosis ◽  
Systemic Chemotherapy ◽  
Treatment Strategies ◽  
Response Assessment ◽  
Low Grade ◽  
High Grade ◽  
Measurable Disease ◽  
Gastric Cancer Patients

e14558 Background: Although many clinical trials of newly developed chemotherapeutic drugs have been conducted, limited studies have focused on gastric cancer patients specifically diagnosed with peritoneal carcinomatosis (PC) without measurable regions. In the current study, we characterized the outcomes of systemic chemotherapy and prognostic factors for patients with gastric cancer PC, particularly in cases without measurable disease. Methods: Clinical data from 211 gastric cancer PC patients (137 without and 74 with measurable disease) subjected to systemic chemotherapy between January 2000 and December 2010 at a single center were reviewed. Results: Median OS rates of gastric cancer PC patients with no measurable disease were significantly longer than those of patients with measurable disease (18.2 vs 12.0 months, p=0.011). In multivariate analysis, poor PS (Hazard ratio (HR) = 2.33, 95% CI, 1.42-3.8, P=0.001), presence of metastatic lymphadenopathy (LAP) (HR=2.23, 95% CI, 1.42-3.5, p=0.002) and high-grade PC (HR=1.82, 95% CI, 1.09-3.04, p=0.025) were associated with significantly decreased OS. Combined with clinical PC grade and measurability of disease, median OS of patients with low-grade PC without measurable disease was 19.6 months (95% CI, 15.5-23.7 months). Median OS rates of 12.6, 13.7 and 6.8 months were estimated in high-grade PC without measurable disease, low-grade PC with measurable disease, and high-grade PC with measurable disease, respectively. Median OS of low-grade PC patients with no measurable disease was significantly higher than that of patients in all other groups (p=0.001, p=0.029 and p<0.001, respectively). Conclusions: Gastric cancer PC is a heterogeneous disease entity. In our study, clinically low-grade PC without measurable disease was associated with better outcomes than other groups following systemic chemotherapy. According to the carcinomatosis grade, specific groups of patients may benefit from systemic chemotherapy. Despite the difficulties of response assessment, further clinical trials for newer treatment strategies and molecular studies focusing on the heterogeneity of gastric cancer PC should be introduced.

scholarly journals Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping He ◽  
Shihuan Cheng ◽  
Feng Hu ◽  
Zhanchuan Ma ◽  
Yan Xia
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cell Line ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Potential Role ◽  
Gastric Cancer Treatment ◽  
Gastric Cancer Patients ◽  
And Function ◽  
Cancer Tissues

Abstract Background Diacylglycerol-acyltransferase 1 (DGAT1) plays an important role in the energy storage and is involved in cancer progression. A growing number of evidences showed that elevated expression of DGAT1 in cancer tissue indicated a poor outcome in cancer patients. However, the relationship between DGAT1 and gastric cancer is still unclear. Thus, Transcriptomic analysis and in vitro experiments were performed to investigate the role of DGAT1 in gastric cancer, as well as the potential therapy target in gastric cancer treatment. Methods We screened the public cancer datasets to identify the expression and function of DGAT1 in gastric cancer and tumor infiltrating lymphocytes. Then we testified the DGAT1 expression and function after sodium oleate treatment in AGS and MKN45 cell line. Finally, we analyzed ration of apoptosis, necrosis in gastric cancer cells by using flow cytometry after administration of DGAT1 inhibitor. Results Our results showed a highly expression of DGAT1 in gastric cancer tissues (n = 5, p = 0.0004), and tumor-infiltrating macrophages with elevated DGAT1 expression is associated with poor overall survival in gastric cancer patients. In addition, gastric cell lines AGS (n = 3, p < 0.05) and MKN45 (n = 3, p < 0.01) expressed higher level of DGAT1 than human gastric mucosal epithelial cell line GES-1. Administration of DGAT1 inhibitor effectively suppressed functional factors expression and induced cell death in MKN45. Conclusion The findings of this research provide an in-depth insight into the potential role and influences involved in DGAT1 in the gastric cancer patients. And higher expression of DGAT1 leads to lower overall survival (OS) rate in patients with poorly differentiated gastric cancer. Our findings suggest a potential role for DGAT1 in the gastric cancer progression and inhibiting DGAT1 might be a promising strategy in gastric cancer treatment.

scholarly journals Application of clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area, a propensity score matching study and comparison with open gastrectomy

2020 ◽  
Author(s):  
Hua Yang ◽  
Wei-Han Zhang ◽  
Kai Liu ◽  
Yu-Qing Dan ◽  
Xin-Zu Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Surgical Treatment ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Cancer Patients ◽  
Final Analysis ◽  
Cancer Surgery ◽  
Open Gastrectomy ◽  
Gastric Cancer Surgery ◽  
Gastric Cancer Patients

Abstract Background Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area. Methods The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups. Results Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28–44.74 vs. 29, IQR 29–39.5, p = 0.002) and no. 9 station nodes (2, IQR 1–5 vs. 2, IQR 1–3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20–80 ml vs. 80, IQR 50–80 ml, p < 0.001) and a longer surgical duration (262.5 min, IQR 220–303.25 min vs. 232, IQR 220–255 min, p < 0.001) in the CML group than in the OG group. The incidence of postoperative complications (19.8% vs. 16.0%, p = 0.591) and postoperative hospital stay (8, IQR 7–9 days vs. 8, IQR 7–9 days, p = 0.452) were comparable between the CML and OG groups. Conclusion Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events.

scholarly journals Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

2020 ◽  
Vol 22 (1) ◽  
pp. 277
Author(s):  
Joanna Kozak ◽  
Alicja Forma ◽  
Marcin Czeczelewski ◽  
Paweł Kozyra ◽  
Elżbieta Sitarz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Epithelial Mesenchymal Transition ◽  
Inorganic Compounds ◽  
Treatment Modalities ◽  
Pharmacological Agents ◽  
Mesenchymal Transition ◽  
Gastric Cancer Treatment ◽  
Induction Of Resistance ◽  
Gastric Cancer Patients

Epithelial-mesenchymal transition (EMT) constitutes one of the hallmarks of carcinogenesis consisting in the re-differentiation of the epithelial cells into mesenchymal ones changing the cellular phenotype into a malignant one. EMT has been shown to play a role in the malignant transformation and while occurring in the tumor microenvironment, it significantly affects the aggressiveness of gastric cancer, among others. Importantly, after EMT occurs, gastric cancer patients are more susceptible to the induction of resistance to various therapeutic agents, worsening the clinical outcome of patients. Therefore, there is an urgent need to search for the newest pharmacological agents targeting EMT to prevent further progression of gastric carcinogenesis and potential metastases. Therapies targeted at EMT might be combined with other currently available treatment modalities, which seems to be an effective strategy to treat gastric cancer patients. In this review, we have summarized recent advances in gastric cancer treatment in terms of targeting EMT specifically, such as the administration of polyphenols, resveratrol, tangeretin, luteolin, genistein, proton pump inhibitors, terpenes, other plant extracts, or inorganic compounds.

Randomized controlled trial of omental bursectomy for resectable cT2-3 gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 72-72 ◽  
Author(s):  
Y. Kurokawa ◽  
Y. Fujiwara ◽  
S. Takiguchi ◽  
J. Fujita ◽  
H. Imamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Randomized Controlled Trial ◽  
Interim Analysis ◽  
Statistical Power ◽  
Controlled Trial ◽  
Final Analysis ◽  
Morbidity Rate ◽  
Randomized Controlled ◽  
Resectable Gastric Cancer ◽  
Gastric Cancer Patients

72 Background: Omental bursectomy, a traditional surgical procedure to dissect the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon, has often been performed against resectable gastric cancer. We have conducted a multi- institutional randomized controlled trial to elucidate the safety and usefulness of this procedure. Methods: Patients with cT2 or cT3 gastric adenocarcinoma were intraoperatively randomized to radical gastrectomy plus D2 lymphadenectomy either with or without bursectomy. The primary endpoint was overall survival (OS). The planned sample size was 464, with an alpha error of 0.05 and statistical power of 80% to detect a 10% margin of non-inferiority for the non-bursectomy group. The first interim analysis was conducted on Sep 2008, and we decided the preliminary data release according to Korn's proposal (J Clin Oncol. 2005). Results: Between Jul 2002 and Jan 2007, a total of 210 patients were randomized to either the bursectomy group or the non-bursectomy group. Background characteristics were well balanced. Intraoperative blood loss was greater in the bursectomy group than in the non-bursectomy group (median, 475 mL vs. 350 mL, p=0.047), while other surgical factors did not vary significantly. The overall morbidity rate was 14%, the same between two groups. The hospital mortality rate was 0.95%; one patient per group. In the first interim analysis, the 3-year OS were 86% in bursectomy group and 79% in non-bursectomy group, and the hazard ratio was 1.55 (95% CI: 0.84-2.84). The non-bursectomy group had more patients with peritoneal recurrences than the bursectomy group (14% vs. 8%). Conclusions: Experienced surgeons could safely perform a D2 gastrectomy with an additional bursectomy. First interim analysis suggested the survival advantage of omental bursectomy for cT2-3 gastric cancer patients. Final analysis will be conducted in 2012. No significant financial relationships to disclose.

scholarly journals The Implication of Autophagy in Gastric Cancer Progression

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1304
Author(s):  
Evangelos Koustas ◽  
Eleni-Myrto Trifylli ◽  
Panagiotis Sarantis ◽  
Nikolaos I. Kontolatis ◽  
Christos Damaskos ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Tumor Promoter ◽  
Molecular Characteristics ◽  
Gastric Cancer Patients

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis, and strategies for clinical management. However, many gastric tumors appear to be resistant to current chemotherapeutic agents. Moreover, a significant number of gastric cancer patients, with a lack of optimal treatment strategies, have reduced survival. In recent years, multiple research data have highlighted the importance of autophagy, an essential catabolic process of cytoplasmic component digestion, in cancer. The role of autophagy as a tumor suppressor or tumor promoter mechanism remains controversial. The multistep nature of the autophagy process offers a wide array of targetable points for designing novel chemotherapeutic strategies. The purpose of this review is to summarize the current knowledge regarding the interplay between gastric cancer development and the autophagy process and decipher the role of autophagy in this kind of cancer. A plethora of different agents that direct or indirect target autophagy may be a novel therapeutic approach for gastric cancer patients.

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