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Frontiers in Oncology 2021Preclinical and clinical antiangiogenic approaches, with multiple side effects such as resistance, have not been proved to be very successful in treating tumor blood... (Review)
Review
Preclinical and clinical antiangiogenic approaches, with multiple side effects such as resistance, have not been proved to be very successful in treating tumor blood vessels which are important targets for tumor therapy. Meanwhile, restoring aberrant tumor blood vessels, known as tumor vascular normalization, has been shown not only capable of reducing tumor invasion and metastasis but also of enhancing the effectiveness of chemotherapy, radiation therapy, and immunotherapy. In addition to the introduction of such methods of promoting tumor vascular normalization such as maintaining the balance between proangiogenic and antiangiogenic factors and targeting endothelial cell metabolism, microRNAs, and the extracellular matrix, the latest molecular mechanisms and the potential connections between them were primarily explored. In particular, the immunotherapy-induced normalization of blood vessels further promotes infiltration of immune effector cells, which in turn improves immunotherapy, thus forming an enhanced loop. Thus, immunotherapy in combination with antiangiogenic agents is recommended. Finally, we introduce the imaging technologies and serum markers, which can be used to determine the window for tumor vascular normalization.
PubMed: 34476218
DOI: 10.3389/fonc.2021.719836 -
Cancer May 2011Cancers in children and adolescents are fortunately infrequent. Overall, cure rates are good, approximately 80%, although this varies by histology and stage. Targeted... (Review)
Review
Cancers in children and adolescents are fortunately infrequent. Overall, cure rates are good, approximately 80%, although this varies by histology and stage. Targeted therapies aim to improve efficacy and decrease toxicity by more specifically affecting malignant cells or their supporting stroma. Cancers of early life are often of different histology than those seen in adults. Sometimes, the same pathway is affected, even if the histology is different. Toxicities may also be different, particularly in younger children. These factors render drug development in young people challenging. This article reviews some successes and challenges to that development, including brief discussions of imatinib, lestaurtinib, antiangiogenesis, and anti-GD2 therapies.
Topics: Adolescent; Angiogenesis Inhibitors; Benzamides; Child; Gangliosides; Humans; Imatinib Mesylate; Molecular Targeted Therapy; Neoplasms; Pharmacokinetics; Piperazines; Pyrimidines; Young Adult; fms-Like Tyrosine Kinase 3
PubMed: 21523745
DOI: 10.1002/cncr.26050 -
Oncology Research and Treatment 2018Angiogenesis, the process leading to the formation of new blood vessels, is one of the hallmarks of cancer. Extensive studies established that i) vascular endothelial... (Review)
Review
Angiogenesis, the process leading to the formation of new blood vessels, is one of the hallmarks of cancer. Extensive studies established that i) vascular endothelial growth factor (VEGF) is a key driver of sprouting angiogenesis, ii) VEGF is overexpressed in most solid cancers, and iii) inhibition of VEGF can suppress tumor growth in animal models. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve the tumor of nutrients and oxygen, primarily through the blockade of VEGF/VEGF receptor signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, either alone or in combination with chemotherapy and other targeted therapies. However, inhibition of VEGF signaling is not effective in all cancers, and anti-angiogenics have often only limited impact on overall survival of cancer patients. This review focuses on the current status of FDA-approved anti-angiogenic antibodies and tyrosine kinase inhibitors and summarizes the progress and future directions of VEGF-targeted therapy.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antineoplastic Agents; Drug Resistance, Neoplasm; Humans; Molecular Targeted Therapy; Neoplasms; Neovascularization, Pathologic; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 29562226
DOI: 10.1159/000488087 -
Review article: gene therapy, recent developments and future prospects in gastrointestinal oncology.Alimentary Pharmacology & Therapeutics Oct 2010Gene therapy consists of the introduction of genetic material into cells for a therapeutic purpose. A wide range of gene therapy vectors have been developed and used for... (Review)
Review
BACKGROUND
Gene therapy consists of the introduction of genetic material into cells for a therapeutic purpose. A wide range of gene therapy vectors have been developed and used for applications in gastrointestinal oncology.
AIM
To review recent developments and published clinical trials concerning the application of gene therapy in the treatment of liver, colon and pancreatic cancers.
METHODS
Search of the literature published in English using the PubMed database.
RESULTS
A large variety of therapeutic genes are under investigation, such as tumour suppressor, suicide, antiangiogenesis, inflammatory cytokine and micro-RNA genes. Recent progress concerns new vectors, such as oncolytic viruses, and the synergy between viral gene therapy, chemotherapy and radiation therapy. As evidence of these basic developments, recently published phase I and II clinical trials, using both single agents and combination strategies, in adjuvant or advanced disease settings, have shown encouraging results and good safety records.
CONCLUSIONS
Cancer gene therapy is not yet indicated in clinical practice. However, basic and clinical advances have been reported and gene therapy is a promising, new therapeutic approach for the treatment of gastrointestinal tumours.
Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colonic Neoplasms; Gastrointestinal Neoplasms; Genetic Therapy; Genetic Vectors; Humans; Immunotherapy; Liver Neoplasms; Models, Biological; Pancreatic Neoplasms; RNA Interference
PubMed: 20937041
DOI: 10.1111/j.1365-2036.2010.04424.x -
Journal of Hematology & Oncology Oct 2019Liver cancer, mostly hepatocellular carcinoma (HCC), is the second leading cause of cancer mortality globally. Most patients need at least one systemic therapy at... (Review)
Review
Liver cancer, mostly hepatocellular carcinoma (HCC), is the second leading cause of cancer mortality globally. Most patients need at least one systemic therapy at different phases of their treatment for HCC. Sorafenib was the first agent shown to improve the survival of patients with advanced HCC. A decade after the approval of sorafenib, most agents failed to improve patient survival more than sorafenib. In recent years, treatment practices have changed, with lenvatinib as another first-line treatment choice and regorafenib, ramucirumab, and cabozantinib as second-line treatment options. Anti-PD-1 antibodies, including nivolumab, pembrolizumab, and camrelizumab, have demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials. The combination of an anti-PD-1 antibody and an anti-angiogenesis agent has shown more potent anti-tumor effects in early phase clinical trials and is now the hotspot in clinical studies. Furthermore, these agents are investigated in combination treatment with surgery or other loco-regional therapies in patients with early or intermediate-stage HCC.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Humans; Immunotherapy; Liver Neoplasms
PubMed: 31655607
DOI: 10.1186/s13045-019-0794-6 -
Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review.Toxins Feb 2021Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects.... (Review)
Review
Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application.
Topics: Animals; Drugs, Chinese Herbal; Endometriosis; Female; Humans; Medicine, East Asian Traditional; Tissue Extracts; Toxins, Biological; Treatment Outcome; Venoms
PubMed: 33673020
DOI: 10.3390/toxins13020145 -
Cold Spring Harbor Perspectives in... Oct 2012The development and use of antiangiogenesis agents, particularly those targeting vascular endothelial growth factor (VEGF), has become an integral component of... (Review)
Review
The development and use of antiangiogenesis agents, particularly those targeting vascular endothelial growth factor (VEGF), has become an integral component of anticancer regimens for many tumor types. This review is intended to highlight some of the most important clinical successes and failures of anti-VEGF therapies, and where possible, to suggest important lessons that have been learned. This review emphasizes data from agents that have been FDA approved and/or have completed phase III studies.
Topics: Angiogenesis Inhibitors; Biomarkers, Tumor; Drug Approval; Humans; Neoplasms; Neovascularization, Pathologic; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 23028128
DOI: 10.1101/cshperspect.a006577 -
Cancers Sep 2022The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing... (Review)
Review
The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct combination therapies, all with survival benefits, and with guideline recommendation for use in the front-line setting. As such, treatment selection has become increasingly complex with a myriad of treatment choices but little high-level head-to-head data to guide treatment selection. Heterogeneity in tumor biology further complicates treatment selection as tumors vary in behavior and treatment responsiveness. Ongoing development of biomarkers will certainly assist in this setting, and validation of predictive markers represents an unmet need. In their absence, we highlight features of disease and nuances to datasets from landmark prospective clinical trials to help inform treatment selection. There is growing evidence to support deferring upfront systemic therapy in some patients, with opportunities for active surveillance or metastasis-directed therapy. In others, upfront systemic therapy is warranted and necessitates thoughtful consideration of multiple clinicopathologic parameters to inform optimal patient-centered decision making.
PubMed: 36230530
DOI: 10.3390/cancers14194607 -
Chinese Journal of Cancer Aug 2010Hypoxia is a common phenomenon in solid tumors. Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors. The... (Review)
Review
Hypoxia is a common phenomenon in solid tumors. Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors. The growth and metastasis of solid tumors rely on blood vessels. Antiangiogenic agents mainly target tumor blood vessels, and radiation therapy mainly targets tumor cells. Combination of antiangiogenic treatment and radiation exhibits synergistic effect, which improves the response of tumors to radiation therapy. The mechanisms of interaction between antiangiogenic agents and ionizing radiation are complex and involve interactions between tumor cells and tumor microenvironment, including tumor oxygenation, stroma, and vasculature. The original mechanism of antiangiogenesis is to induce ischemia and hypoxia in tumors, thereby, "starve" the tumors. However, recently, emerging data suggest that antiangiogenic agents could reduce the proportion of hypoxic cells through normalizing tumor vasculature, decreasing oxygen consumption, and other mechanisms. The use of antiangiogenic agents provides a new approach to overcome the hypoxia problem, and ultimately improves the efficacy of radiation therapy. In this review, we discuss tumor hypoxia, tumor angiogenesis and its regulation, mechanisms of antiangiogenic therapy combined with radiation therapy, and how antiangiogenic therapy overcomes tumor hypoxia.
Topics: Angiogenesis Inhibitors; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Apoptosis; Bevacizumab; Cell Hypoxia; Combined Modality Therapy; Endostatins; Humans; Neoplasms; Neovascularization, Pathologic; Oxygen Consumption
PubMed: 20663317
DOI: 10.5732/cjc.010.10010 -
Molecular Medicine Reports Mar 2024Endometriosis (EM) is one of the most common diseases among women of reproductive age. The etiology and pathogenesis of EM remain unclear and therefore there is a lack... (Review)
Review
Endometriosis (EM) is one of the most common diseases among women of reproductive age. The etiology and pathogenesis of EM remain unclear and therefore there is a lack of effective treatment measures, which affects physical and mental health, as well as the quality of life of patients with EM. Angiogenesis has become a hotspot for research on the pathogenesis of EM; the role of angiogenesis‑related serological markers and anti‑angiogenic therapy in the diagnosis and treatment of EM is promising for early diagnosis and treatment of EM. Angiogenesis in EM is subject to complex regulation by hormones, immunity and associated cytokines. Therefore, novel targets for angiogenesis therapy are also being discovered and developed. The present review summarized the pathological mechanisms of angiogenesis and the value of relevant markers in pathogenesis and diagnosis of EM, along with the status of research on anti‑angiogenic drugs in the treatment of EM. The role of angiogenesis in EM provides an important reference for treatment and diagnosis, but there is no uniform non‑invasive diagnostic marker and proven strategy for anti‑angiogenesis.
Topics: Humans; Female; Endometriosis; Angiogenesis; Quality of Life; Cytokines; Immunotherapy
PubMed: 38240108
DOI: 10.3892/mmr.2024.13167