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Signal Transduction and Targeted Therapy May 2023Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- and anti-angiogenic molecules, which plays a crucial role in... (Review)
Review
Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- and anti-angiogenic molecules, which plays a crucial role in tumor growth, invasion, and metastasis. With the advances in molecular and cellular biology, various biomolecules such as growth factors, chemokines, and adhesion factors involved in tumor angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules has driven anti-angiogenic treatment to become a promising strategy in anti-tumor therapy. The most widely used anti-angiogenic agents include monoclonal antibodies and tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) pathway. However, the clinical benefit of this modality has still been limited due to several defects such as adverse events, acquired drug resistance, tumor recurrence, and lack of validated biomarkers, which impel further research on mechanisms of tumor angiogenesis, the development of multiple drugs and the combination therapy to figure out how to improve the therapeutic efficacy. Here, we broadly summarize various signaling pathways in tumor angiogenesis and discuss the development and current challenges of anti-angiogenic therapy. We also propose several new promising approaches to improve anti-angiogenic efficacy and provide a perspective for the development and research of anti-angiogenic therapy.
Topics: Humans; Vascular Endothelial Growth Factor A; Neoplasms; Neovascularization, Pathologic; Angiogenesis Inhibitors; Signal Transduction
PubMed: 37169756
DOI: 10.1038/s41392-023-01460-1 -
Angiogenesis Nov 2022While inhibiting pathological angiogenesis has been long associated with the field of oncology, recent advances in angiogenesis research have impacted the progress of...
While inhibiting pathological angiogenesis has been long associated with the field of oncology, recent advances in angiogenesis research have impacted the progress of disease treatment for additional non-malignant diseases or chronic conditions in the fields of ophthalmology, cardiology, and gynecology. Moreover, stimulators of angiogenesis find application in ischemic diseases, while inhibitors of angiogenesis are being used to limit blood vessel formation, but in judicious ways that modify or "reprogram" the vasculature as a reinforcement for immunotherapy. We have noticed an increasing impact, as evidenced by increases in the total number of citations, in the literature surrounding the angiogenesis field suggesting that targeting angiogenesis per se is well established as a tractable approach for therapy in diverse conditions.
Topics: Angiogenesis Inhibitors; Humans; Immunotherapy; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 35881257
DOI: 10.1007/s10456-022-09849-2 -
Cancer Treatment Reviews Jun 2020When the VEGF-A-targeting monoclonal antibody bevacizumab (Avastin®) entered clinical practice more than 15 years ago, it was one of the first targeted therapies and... (Review)
Review
When the VEGF-A-targeting monoclonal antibody bevacizumab (Avastin®) entered clinical practice more than 15 years ago, it was one of the first targeted therapies and the first approved angiogenesis inhibitor. Marking the beginning for a new line of anti-cancer treatments, bevacizumab remains the most extensively characterized anti-angiogenetic treatment. Initially approved for treatment of metastatic colorectal cancer in combination with chemotherapy, its indications now include metastatic breast cancer, non-small-cell lung cancer, glioblastoma, renal cell carcinoma, ovarian cancer and cervical cancer. This review provides an overview of the clinical experience and lessons learned since bevacizumab's initial approval, and highlights how this knowledge has led to the investigation of novel combination therapies. In the past 15 years, our understanding of VEGF's role in the tumor microenvironment has evolved. We now know that VEGF not only plays a major role in controlling blood vessel formation, but also modulates tumor-induced immunosuppression. These immunomodulatory properties of bevacizumab have opened up new perspectives for combination therapy approaches, which are being investigated in clinical trials. Specifically, the combination of bevacizumab with cancer immunotherapy has recently been approved in non-small-cell lung cancer and clinical benefit was also demonstrated for treatment of hepatocellular carcinoma. However, despite intense investigation, reliable and validated biomarkers that would enable a more personalized use of bevacizumab remain elusive. Overall, bevacizumab is expected to remain a key agent in cancer therapy, both due to its established efficacy in approved indications and its promise as a partner in novel targeted combination treatments.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents, Immunological; Bevacizumab; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Molecular Targeted Therapy; Neoplasms; Neovascularization, Pathologic; Randomized Controlled Trials as Topic
PubMed: 32335505
DOI: 10.1016/j.ctrv.2020.102017 -
Anti-cancer Agents in Medicinal... 2018The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical... (Review)
Review
The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents, Phytogenic; Cell Proliferation; Humans; Neoplasms; Polysaccharides; Reishi
PubMed: 29141563
DOI: 10.2174/1871520617666171113121246 -
Pharmacology & Therapeutics Feb 2018Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of... (Review)
Review
Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of cancer. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy and lead to other cardiovascular complications. The factors that contribute to interindividual variability in blood pressure response to bevacizumab treatment are not well understood. In this review, we outline research efforts to understand the mechanisms and pathophysiology of hypertension resulting from bevacizumab treatment. Moreover, we highlight current knowledge of the pharmacogenetics of bevacizumab-induced hypertension, which may be used to develop strategies to prevent or minimize this toxicity.
Topics: Angiogenesis Inhibitors; Animals; Antibodies, Monoclonal, Humanized; Bevacizumab; Humans; Hypertension; Models, Cardiovascular; Vasodilation
PubMed: 28882537
DOI: 10.1016/j.pharmthera.2017.08.012 -
Cell Proliferation Apr 2021The sites of targeted therapy are limited and need to be expanded. The FGF-FGFR signalling plays pivotal roles in the oncogenic process, and FGF/FGFR inhibitors are a... (Review)
Review
The sites of targeted therapy are limited and need to be expanded. The FGF-FGFR signalling plays pivotal roles in the oncogenic process, and FGF/FGFR inhibitors are a promising method to treat FGFR-altered tumours. The VEGF-VEGFR signalling is the most crucial pathway to induce angiogenesis, and inhibiting this cascade has already got success in treating tumours. While both their efficacy and antitumour spectrum are limited, combining FGF/FGFR inhibitors with VEGF/VEGFR inhibitors are an excellent way to optimize the curative effect and expand the antitumour range because their combination can target both tumour cells and the tumour microenvironment. In addition, biomarkers need to be developed to predict the efficacy, and combination with immune checkpoint inhibitors is a promising direction in the future. The article will discuss the FGF-FGFR signalling pathway, the VEGF-VEGFR signalling pathway, the rationale of combining these two signalling pathways and recent small-molecule FGFR/VEGFR inhibitors based on clinical trials.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Fibroblast Growth Factors; Humans; Neoplasms; Polymorphism, Single Nucleotide; Receptors, Fibroblast Growth Factor; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 33655556
DOI: 10.1111/cpr.13009 -
Hypertension (Dallas, Tex. : 1979) Mar 2023Contemporary anticancer drugs have significantly improved cancer survival at the expense of cardiovascular toxicities, including heart disease, thromboembolic disease,... (Review)
Review
Contemporary anticancer drugs have significantly improved cancer survival at the expense of cardiovascular toxicities, including heart disease, thromboembolic disease, and hypertension. One of the most common side effects of these drugs is hypertension, especially in patients treated with vascular endothelial growth factor inhibitors, as well as tyrosine kinase inhibitors and proteasome inhibitors. Adjunctive therapy, including corticosteroids, calcineurin inhibitors, and nonsteroidal anti-inflammatories, as well as anti-androgen hormone therapy for prostate cancer, may further increase blood pressure in these patients. Cancer therapy-induced hypertension is often dose limiting, increases cardiovascular mortality in cancer survivors, and is usually reversible after interruption or discontinuation of treatment. The exact molecular mechanisms underlying hypertension are unclear, but recent discoveries indicate an important role for reduced nitric oxide generation, oxidative stress, endothelin-1, prostaglandins, endothelial dysfunction, increased sympathetic outflow, and microvascular rarefaction. In addition, genetic polymorphisms in vascular endothelial growth factor receptors are implicated in vascular endothelial growth factor inhibitor-induced hypertension. Diagnosis, management, and follow-up of cancer therapy-induced hypertension follow national hypertension guidelines because evidence-based clinical trials specifically addressing patients who develop hypertension as a result of cancer therapy are currently lacking. Rigorous baseline assessment of patients before therapy is started requires particular emphasis on assessing and treating cardiovascular risk factors. Hypertension management follows guidelines for the general population, although special attention should be given to rebound hypotension after termination of cancer therapy. Management of these complex patients requires collaborative care involving oncologists, cardiologists, hypertension specialists, primary care professionals, and pharmacists to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.
Topics: Male; Humans; Vascular Endothelial Growth Factor A; American Heart Association; Hypertension; Antineoplastic Agents; Angiogenesis Inhibitors; Neoplasms
PubMed: 36621810
DOI: 10.1161/HYP.0000000000000224 -
Expert Opinion on Therapeutic Targets Jan 2022Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among people age 60 years or older in developed countries. Current... (Review)
Review
INTRODUCTION
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among people age 60 years or older in developed countries. Current standard-of-care anti-vascular endothelial growth factor (VEGF) therapy, which inhibits angiogenesis and vascular permeability, has been shown to stabilize choroidal neovascularization and increase visual acuity in neovascular AMD. However, therapeutic limitations of anti-VEGF therapy include limited durability with consequent need for frequent intravitreal injections, and a ceiling of efficacy. Current strategies under investigation include targeting VEGF-C and VEGF-D, integrins, tyrosine kinase receptors, and the Tie2/angiopoietin-2 pathway. A literature search was conducted through November 30, 2021 on PubMed, Medline, Google Scholar, and associated digital platforms with the following keywords: wet macular degeneration, age-related macular degeneration, therapy, VEGF-A, VEGF-C, VEGF-D, integrins, Tie2/Ang2, and tyrosine kinase inhibitors.
AREAS COVERED
The authors provide a comprehensive review of AMD disease pathways and mechanisms involved in wet AMD as well as novel targets for future therapies.
EXPERT OPINION
With novel targets and advancements in drug delivery, there is potential to address treatment burden and to improve outcomes for patients afflicted with neovascular AMD.
Topics: Angiogenesis Inhibitors; Disease Progression; Humans; Middle Aged; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration
PubMed: 35060431
DOI: 10.1080/14728222.2022.2030706 -
Molecular Cancer Mar 2022Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to...
BACKGROUND
Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients.
METHODS
We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes.
RESULTS
CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2-92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival.
CONCLUSION
This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Biomarkers, Tumor; Humans; Neovascularization, Pathologic; Programmed Cell Death 1 Receptor; Triple Negative Breast Neoplasms
PubMed: 35337339
DOI: 10.1186/s12943-022-01536-6 -
International Journal of Molecular... Sep 2016Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver... (Review)
Review
Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs.
Topics: Angiogenesis Inhibitors; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Green Chemistry Technology; Humans; Metal Nanoparticles; Silver
PubMed: 27649147
DOI: 10.3390/ijms17091534