Coagulation is a highly conserved process occurring after an injury to a blood vessel and resulting in hemostasis. In the thrombus microenvironment, finely orchestrated events restore vessel ...integrity through platelet activation, adhesion, and aggregation (primary hemostasis), followed by the coagulation cascades, thrombin generation, and fibrin clot deposition (secondary hemostasis). Several studies on cancer have provided insight into dramatic changes to coagulation‐related events (i.e., fibrin clot deposition, fibrinolysis) during tumor pathogenesis, progression, and metastasis, in addition to a tumor‐driven systemic activation of hemostasis and thrombosis (Trousseau's syndrome). Diverse molecular and cellular effectors participate in the cross talk between hemostasis and tumors. Here, we focus on some aspects of the interconnection between cancer biology and hemostatic components, with particular attention to some key coagulation‐related proteins (e.g., tissue factor, thrombin, fibrinogen, and D‐dimers) in the particular case of gastric cancer (GC). Recent advances in deciphering the complex molecular link between GC and the coagulation system are described, showing their important roles in better management of patients affected by GC.
: Angiogenesis inhibitors have become an important therapeutic approach in the treatment of hepatocellular carcinoma (HCC) patients. The therapeutic inhibition of angiogenesis of Sorafenib in ...increasing overall survival of patients with HCC is a fundamental element of the treatment of this disease. Considering the heterogeneous aspects of HCC and to boost therapeutic efficacy, prevail over drug resistance and lessen toxicity, adding antiangiogenic drugs to antiblastic chemotherapy (AC), radiation therapy or other targeted drugs have been evaluated. The matter is additionally complicated by the combination of antiangiogenesis with further AC or biologic drugs. To date, no planned approach to understand which patients are more responsive to a given type of antiangiogenic treatment is available.
: Large investments in the clinical research are essential to improve treatment response and minimize toxicities for patients with HCC. Future investigations will need to focus on utilizing patterns of genetic information to classify HCC into groups that display similar prognosis and treatment sensitivity, and combining targeted therapies with AC producing enhanced anti-tumor effect. In this review the current panel of available antiangiogenic therapies for the treatment of HCC have been analyzed. In addition current clinical trials are also reported herein.
One of the hallmarks of cancer is angiogenesis, a series of events leading to the formation of the abnormal vascular network required for tumor growth, development, progression, and metastasis. ...MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs whose functions include modulation of the expression of pro- and anti-angiogenic factors and regulation of the function of vascular endothelial cells. Vascular-associated microRNAs can be either pro- or anti-angiogenic. In cancer, miRNA expression levels are deregulated and typically vary during tumor progression. Experimental data indicate that the tumor phenotype can be modified by targeting miRNA expression. Based on these observations, miRNAs may be promising targets for the development of novel anti-angiogenic therapies. This review discusses the role of various miRNAs and their targets in tumor angiogenesis, describes the strategies and challenges of miRNA-based anti-angiogenic therapies and explores the potential use of miRNAs as biomarkers for anti-angiogenic therapy response.
Background & Aims
A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for ...HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option.
Methods
Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels.
Results
Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50–0.79), cabozantinib (HR = 0.76, 95% CI = 0.63–0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70–0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36–0.52), regorafenib (HR = 0.46, 95% CI = 0.37–0.56), ramucirumab (HR = 0.54, 95% CI = 0.43–0.68), brivanib (HR = 0.56, 95% CI = 0.42–0.76), S-1 (HR = 0.60, 95% CI = 0.46–0.77), axitinib (HR = 0.62, 95% CI = 0.44–0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57–0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients’ stratification.
Conclusions
The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.
Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Stomach cancers are ...90% adenocarcinoma; lymphoma, carcinoid, and stromal tumours may occur. Adenocarcinoma can be subdivided into histological Lauren and the World Health Organization (WHO) classifications, but this information has not led to the development of histologic subtype-specific treatment options. One way to potentially improve treatment for gastric cancers is to better understand the pathogenesis of this disease, the contribution of Helicobacter pylori infection, and host immune response to lead to the development of integrated histological and molecular classification schemes for gastric cancer. The hope is that these studies may facilitate the development of clinical trials to explore therapies in defined sets of patients, ultimately improving survival from this deadly disease.
Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, ...the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differences in GC and have led to the identification of an Epstein-Barr virus (EBV)-related GC subtype (EBVaGC), providing new indications for tailored treatment and prognostic factors. This article provides a review of the features of EBVaGC and an update on the latest insights from EBV-related research with a particular focus on the strict interaction between EBV infection and the gastric tumor environment, including the host immune response. This information may help increase our knowledge of EBVaGC pathogenesis and the mechanisms that sustain the immune response of patients since this mechanism has been demonstrated to offer a survival advantage in a proportion of patients with GC.
Over the last decade, our understanding of the mechanisms underlying immune modulation has greatly improved, allowing for the development of multiple therapeutic approaches that are revolutionizing ...the treatment of cancer. Immunotherapy for gastric cancer (GC) is still in the early phases but is rapidly evolving. Recently, multi-platform molecular analyses of GC have proposed a new classification of this heterogeneous group of tumors, highlighting subset-specific features that may more reliably inform therapeutic choices, including the use of new immunotherapeutic drugs. The clinical benefit and improved survival observed in GC patients treated with immunotherapeutic strategies and their combination with conventional therapies highlighted the importance of the immune environment surrounding the tumor. A thorough investigation of the tumor microenvironment and the complex and dynamic interaction between immune cells and tumor cells is a fundamental requirement for the rational design of novel and more effective immunotherapeutic approaches. This review summarizes the pre-clinical and clinical results obtained so far with immunomodulatory and immunotherapeutic treatments for GC and discusses the novel combination strategies that are being investigated to improve the personalization and efficacy of GC immunotherapy.
Background
Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins ...whose expression levels are altered in this disease and also in GC.
Methods
Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5,
P
< 0.01) were selected and identified by LC–MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with
Helicobacter pylori
infection) and from GC patients and unaffected first-degree relatives of GC patients.
Results
2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC–MS/MS identified these as 53 distinct proteins. The most significant (adjusted
P
< 0.01) biological process associated with the less abundant proteins was “tricarboxylic acid cycle”. Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of
H. pylori
infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (
PDIA3, GSTP
gene products) and four less abundant proteins (
ATP5F1A, PGA3, SDHB, PGC
).
Conclusion
This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.
Gastric cancer (GC) is a common malignant neoplasm worldwide and one of the main cause of cancer-related deaths. Despite some advances in therapies, long-term survival of patients with advanced ...disease remains poor. Different types of classification have been used to stratify patients with GC for shaping prognosis and treatment planning. Based on new knowledge of molecular pathways associated with different aspect of GC, new pathogenetic classifications for GC have been and continue to be proposed. These novel classifications create a new paradigm in the definition of cancer biology and allow the identification of relevant GC genomic subsets by using different techniques such as genomic screenings, functional studies and molecular or epigenetic characterization. An improved prognostic classification for GC is essential for the development of a proper therapy for a proper patient population. The aim of this review is to discuss the state-of-the-art on combining histological and molecular classifications of GC to give an overview of the emerging therapeutic possibilities connected to the latest discoveries regarding GC.
PDF
