Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The role of anti-angiogenesis in non-small-cell lung cancer: an update.

ABSTRACT: Recognition of the vascular endothelial growth factor (VEGF) pathway as a key mediator of angiogenesis has led to the clinical study of several VEGF and VEGF receptor (VEGFR) targeted therapies in non-small-cell lung cancer (NSCLC). These targeted therapies include neutralizing antibodies to VEGF (bevacizumab and aflibercept) and VEGFR-2 (ramucirumab) and tyrosine kinase inhibitors (TKIs) with selectivity for the VEGFRs. Bevacizumab and ramucirumab are associated with survival advantages in the treatment of advanced NSCLC: bevacizumab in the first-line setting in combination with carboplatin/paclitaxel and ramucirumab in combination with docetaxel in the second-line setting. The VEGFR-2 TKIs have been associated with responses and improved progression-free survival in selected NSCLC settings; however, this level of activity has thus far been insufficient to confer significant survival advantages. This review will focus on the current state of VEGF targeted therapies in NSCLC.

SUBMITTER: Villaruz LC

PROVIDER: S-EPMC4836185 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The role of anti-angiogenesis in non-small-cell lung cancer: an update.

Villaruz Liza C LC Socinski Mark A MA

Current oncology reports 20150601 6

Recognition of the vascular endothelial growth factor (VEGF) pathway as a key mediator of angiogenesis has led to the clinical study of several VEGF and VEGF receptor (VEGFR) targeted therapies in non-small-cell lung cancer (NSCLC). These targeted therapies include neutralizing antibodies to VEGF (bevacizumab and aflibercept) and VEGFR-2 (ramucirumab) and tyrosine kinase inhibitors (TKIs) with selectivity for the VEGFRs. Bevacizumab and ramucirumab are associated with survival advantages in the ...[more]

PMID: 25947099

Similar Datasets

HIF, hypoxia and the role of angiogenesis in non-small cell lung cancer.

Project description:The role of angiogenesis in the initiation and progression of NSCLC and the molecular alterations leading to the growth of tumor vasculature are areas of great interest and recent therapeutic success.VEGF and its receptors play critical roles in the development of tumor vasculature and can be targeted by agents such as bevacizumab in the treatment of NSCLC. Furthermore, tumor hypoxia and the expression of the hypoxia-inducible factor (HIF) family of proteins are also linked to poorer survival in these patients. Recent studies using genetically engineered mouse models expressing stabilized HIF validate the importance of HIF in the evolution of NSCLC and demonstrate genetically that HIF is involved in NSCLC.An overview of the key pathways and mediators of tumor angiogenesis, their relevance to the pathogenesis of NSCLC, and an update on the current status of angiogenesis inhibitors in NSCLC.Angiogenesis is a key mediator of NSCLC progression. Several antiangiogenic strategies are in clinical use and under development. While candidate predictive biomarkers of response to antiangiogenic therapy exist, they await independent and prospective validation.

| S-EPMC3646329 | biostudies-other

Targeting angiogenesis in squamous non-small cell lung cancer.

Project description:Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and can be further classified as nonsquamous carcinoma (including adenocarcinoma, which accounts for 40 % of NSCLCs) and squamous NSCLC, which makes up 30 % of NSCLC cases. The emergence of inhibitors of epidermal growth factor receptors, anaplastic lymphoma kinase, and vascular endothelial growth factors (VEGF) in the last decade has resulted in steady improvement in clinical outcomes for patients with advanced lung adenocarcinoma. However, improvements in the survival of patients with squamous NSCLC have remained elusive, presenting an urgent need for understanding and investigating therapeutically relevant molecular targets, specifically in squamous NSCLC. Although anti-VEGF therapy has been studied in squamous NSCLC, progress has been slow, in part due to issues related to pulmonary hemorrhage. In addition to these safety concerns, several phase III trials that initially included patients with squamous NSCLC failed to demonstrate improved overall survival (primary endpoint) with the addition of antiangiogenic therapy to chemotherapy compared with chemotherapy alone. Angiogenesis is an established hallmark of tumor progression and metastasis, and the role of VEGF signaling in angiogenesis is well established. However, some studies suggest that, while inhibiting VEGF signaling may be beneficial, prolonged exposure to VEGF/VEGF receptor (VEGFR) inhibitors may allow tumor cells to utilize alternative angiogenic mechanisms and become resistant. As a result, agents that target multiple angiogenic pathways simultaneously are also under evaluation. This review focuses on current and investigational antiangiogenic targets in squamous NSCLC, including VEGF/VEGFRs, fibroblast growth factor receptors, platelet-derived growth factor receptors, and angiopoietin. Additionally, clinical trials investigating VEGF- and multi-targeted antiangiogenic therapies are discussed.

| S-EPMC4014113 | biostudies-literature

Targeting angiogenesis in advanced non-small cell lung cancer.

Project description:Lung cancer is the leading cause of cancer-related mortality in the United States. Over the past 40 years, treatments with standard chemotherapy agents have not resulted in substantial improvements in long-term survival for patients with advanced lung cancer. Therefore, new targets have been sought, and angiogenesis is a promising target for non-small cell lung cancer (NSCLC). Bevacizumab, a monoclonal antibody targeted against the vascular endothelial growth factor, is the only antiangiogenic agent currently recommended by NCCN for the treatment of advanced NSCLC. However, several antibody-based therapies and multitargeted tyrosine kinase inhibitors are currently under investigation for the treatment of patients with NSCLC. This article summarizes the available clinical trial data on the efficacy and safety of these agents in patients with advanced lung cancer.

| S-EPMC6628716 | biostudies-literature

Strategies targeting angiogenesis in advanced non-small cell lung cancer.

Project description:Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy. Numerous oral multitargeting angiogenic small molecule tyrosine kinase inhibitors (TKIs) have been widely evaluated in advanced NSCLC, but only nintedanib in combination with platinum-based doublet chemotherapy has demonstrated a survival benefit in the second-line setting. Additionally, small-molecule TKIs remain the standard of care for patients with mutated EGFR, ALK or ROS1. Moreover, immune checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) are changing the current strategy in the treatment of advanced NSCLC without driver gene mutations. The potential synergistic activity of antiangiogenic agents and TKIs or immunotherapy is an interesting topic of research. This review will summarize the novel antiangiogenic agents, antiangiogenic monotherapy, as well as potential combination therapeutic strategies for the clinical management of advanced NSCLC.

| S-EPMC5581155 | biostudies-literature

Immunotherapy in non-small cell lung cancer: Update and new insights.

Project description:BackgroundThe treatment of non-small-cell lung carcinoma (NSCLC) has changed markedly in recent years as a result of two major treatment milestones: Targeted therapy and immunotherapy. Since 2015, immunotherapy has been changing the paradigm of NSCLC treatment in different settings and has contributed to improve the quality of life of these patients. The most widely used immunotherapy strategy in clinical practice is currently PD-1 and CTLA-4 immune checkpoint inhibition-based immunotherapy. Initial successful results came from an improvement in overall survival for pretreated patients, and immunotherapy subsequently moved to a first-line palliative setting as monotherapy, in combination with chemotherapy or as double-checkpoint inhibition. With regard to earlier stages, consolidation immunotherapy after chemoradiation has also changed the paradigm of unresectable NSCLC, with marked benefits in terms of disease-free and overall survival. During the last few years, efforts have focused on the introduction of immunotherapy in earlier stages as neoadjuvant treatment for potentially resectable tumors and in an adjuvant setting, with some very promising results.AimIn this manuscript, we provide both an agile and thorough review of the role of immunotherapy in non-small cell lung cancer, a critical analysis of the most important studies, current indications, the role of biomarkers, new insights, and future challenges.Relevance for patientsImmunotherapy has revolutionized the treatment of non-small cell lung cancer patients reaching better survival outcomes in first and second palliative setting and in unresectable stage III tumors. Next year's immunotherapy will also introduce in earlier stages. Through an extensive knowledge of the mechanisms of action and of immunotherapy-based studies, the best treatment alternative can be offered to patients, helping to improve their survival and cure rates.

| S-EPMC8177026 | biostudies-literature

Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives.

Project description:Non-small cell lung cancer (NSCLC) still constitutes the most common cancer-related cause of death worldwide. All efforts to introduce suitable treatment options using chemotherapeutics or targeted therapies have, up to this point, failed to exhibit a substantial effect on the 5-year-survival rate. The involvement of epigenetic alterations in the evolution of different cancers has led to the development of epigenetics-based therapies, mainly targeting DNA methyltransferases (DNMTs) and histone-modifying enzymes. So far, their greatest success stories have been registered in hematologic neoplasias. As the effects of epigenetic single agent treatment of solid tumors have been limited, the investigative focus now lies on combination therapies of epigenetically active agents with conventional chemotherapy, immunotherapy, or kinase inhibitors. This review includes a short overview of the most important preclinical approaches as well as an extensive discussion of clinical trials using epigenetic combination therapies in NSCLC, including ongoing trials. Thus, we are providing an overview of what lies ahead in the field of epigenetic combinatory therapies of NSCLC in the coming years.

| S-EPMC5193491 | biostudies-other

Molecularly targeted therapies in non-small-cell lung cancer annual update 2014.

Project description:There have been significant advances in the understanding of the biology and treatment of non-small-cell lung cancer (NSCLC) during the past few years. A number of molecularly targeted agents are in the clinic or in development for patients with advanced NSCLC. We are beginning to understand the mechanisms of acquired resistance after exposure to tyrosine kinase inhibitors in patients with oncogene addicted NSCLC. The advent of next-generation sequencing has enabled to study comprehensively genomic alterations in lung cancer. Finally, early results from immune checkpoint inhibitors are very encouraging. This review summarizes recent advances in the area of cancer genomics, targeted therapies, and immunotherapy.

| S-EPMC4346098 | biostudies-literature

Itraconazole inhibits angiogenesis and tumor growth in non-small cell lung cancer.

Project description:The antiangiogenic agent bevacizumab has been approved for the treatment of non-small cell lung cancer (NSCLC), although the survival benefit associated with this agent is marginal, and toxicities and cost are substantial. A recent screen for selective inhibitors of endothelial cell proliferation identified the oral antifungal drug itraconazole as a novel agent with potential antiangiogenic activity. In this article, we define and characterize the antiangiogenic and anticancer activities of itraconazole in relevant preclinical models of angiogenesis and lung cancer. Itraconazole consistently showed potent, specific, and dose-dependent inhibition of endothelial cell proliferation, migration, and tube formation in response to both VEGF- and basic fibroblast growth factor-mediated angiogenic stimulation. In vivo, using primary xenograft models of human NSCLC, oral itraconazole showed single-agent growth-inhibitory activity associated with induction of tumor hypoxia-inducible factor 1 alpha expression and marked inhibition of tumor vascularity. Itraconazole significantly enhanced the antitumor efficacy of the chemotherapeutic agent cisplatin in the same model systems. Taken together, these data suggest that itraconazole has potent and selective inhibitory activity against multiple key aspects of tumor-associated angiogenesis in vitro and in vivo, and strongly support clinical translation of its use. Based on these observations, we have initiated a randomized phase II study comparing the efficacy of standard cytotoxic therapy with or without daily oral itraconazole in patients with recurrent metastatic NSCLC.

| S-EPMC3206167 | biostudies-literature

Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients.

Project description:An immunohistochemical analysis for E(epithelial)-cadherin and N(neural)-cadherin expression in relation to tumour angiogenesis was performed in 150 patients with nonsmall cell lung cancer (NSCLC). In all, 71 carcinomas (47.3%) were E-cadherin-negative. Epithelial-cadherin-negative tumours had lymph node metastases significantly more frequently than E-cadherin-positive tumours (P=0.0100). On the other hand, 46 carcinomas (30.7%) were N-cadherin-positive. Regarding tumour vascularity, there was no significant correlation between E-cadherin expression and tumour vascular. In contrast, the frequency of hypervascular tumours was significantly higher for N-cadherin-positive carcinomas than for N-cadherin-negative carcinomas (P=0.0373). Regarding prognosis, the 5-year survival rate of patients with E-cadherin-negative NSCLCs was significantly lower than that of patients with E-cadherin-positive NSCLCs (P=0.0146). In contrast, of the patients with large cell carcinomas, the 5-year survival rate of patients with N-cadherin-positive tumours was significantly lower than that of patients with N-cadherin-negative tumours (P=0.0013). A multivariate analysis demonstrated that E-cadherin status (P=0.0339) and tumour vascularity (P=0.0295) were significant indicators for survival. In conclusion, E-cadherin expression and tumour vascularity are significant prognostic factors of NSCLC patients. Furthermore, N-cadherin expression is associated with tumour angiogenesis, and its expression is one of prognostic factors of patients with large cell carcinomas. Thus, N-cadherin also might play a specific role in undifferentiated large cell carcinomas.

| S-EPMC2377142 | biostudies-other

DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small cell lung cancer

Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To understand more about the cellular responses regulated by DUSP1 in NSCLC cells, we interfered DUSP1 expression in the NSCLC cell line H460 and studied the changes in gene expression differentially regulated by this phosphatase. Keywords: Expression profiling by array in cells with genetic modification The human non small lung cancer cell line H460 used in this study was from ATCC (American Type Culture Collection). The cell line was maintained in RPMI (Gibco, Invitrogen) supplemented with 10% bovine serum and transfected by Lipofectamine Plus Reagent from Life Technologies as directed by the manufacturer. The DUSP1 pSuperRetro-derived vectors were constructed as described (Chattoppadhyay et al., 2006). Clones expressing siRNA for DUSP1 were selected for their ability to grow in the presence of puromycin and kept for selection. Stable transfection was confirmed by Western blotting. RNA was extracted and quality control was checked before hybridization on Affymetrix microarrays.

| S-ECPF-GEOD-19592 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data