Angiogenic signaling pathways and anti-angiogenic therapy for cancer

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 11, 2023

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- anti-angiogenic molecules, which plays crucial role in tumor growth, invasion, metastasis. With advances molecular cellular biology, biomolecules such as growth factors, chemokines, adhesion factors involved angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules driven treatment to become promising strategy anti-tumor therapy. The most widely used agents include monoclonal antibodies tyrosine kinase inhibitors (TKIs) targeting vascular endothelial factor (VEGF) pathway. However, clinical benefit this modality still limited due several defects adverse events, acquired drug resistance, recurrence, lack validated biomarkers, impel further mechanisms angiogenesis, development multiple drugs combination therapy figure out how improve efficacy. Here, we broadly summarize signaling pathways discuss current challenges We also propose approaches efficacy provide perspective for

Language: Английский

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Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Sept. 26, 2022

The major concept of "oxidative stress" is an excess elevated level reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption oxygen. precise harmonization oxidative stresses between mitochondria other organelles in the cell absolutely vital to survival. Under stress, ROS produced mediator for tumorigenesis different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, immunoescape allow cancer cells adapt rigorous environment. Accordingly, dynamic balance not only orchestrate complex signaling events but also affect components tumor microenvironment (TME). Immune cells, M2 macrophages, dendritic T immunosuppressive TME ROS-induced inflammation. Based on this notion, numerous strategies mitigate tumors have been tested prevention or therapies; however, these manipulations devised sources mechanisms without established effectiveness. Herein, we integrate current progress regarding impact mitochondrial TME, immune discuss combination emerging ROS-modulating with immunotherapies achieve antitumor effects.

Language: Английский

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Targeting the tumor stroma for cancer therapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 2, 2022

Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part the tumor microenvironment, stroma is highly dynamic, heterogeneous commonly tumor-type specific, it mainly includes noncellular compositions such as extracellular matrix unique cancer-associated vascular system well a wide variety cellular components including activated fibroblasts, mesenchymal cells, pericytes. All these elements operate with each other in coordinated fashion collectively promote initiation, progression, metastasis therapeutic resistance. Over past few decades, numerous studies have been conducted to study interaction crosstalk between neoplastic cells. Meanwhile, we also witnessed exponential increase investigation recognition critical roles solid tumors. A series clinical trials targeting launched continually. In this review, introduce discuss current advances understanding various their cancers. We elaborate on potential novel approaches for tumor-stroma-based targeting, aim leap from bench bedside.

Language: Английский

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Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 25, 2022

Angiogenesis is a vital process for the growth and dissemination of solid cancers. Numerous molecular pathways are known to drive angiogenic switch in cancer cells promoting new blood vessels increased incidence distant metastasis. Several angiogenesis inhibitors clinically available treatment different types advanced These mostly belong monoclonal antibodies or small-molecule tyrosine kinase targeting classical vascular endothelial factor (VEGF) its receptors. Nevertheless, breast one example tumors that had constantly failed respond terms improved survival outcomes patients. Accordingly, it paramount importance assess mechanisms driving signaling explore suitable drug targets can be further investigated preclinical clinical settings. This review summarizes current evidence effect anti-angiogenic drugs treatment. Further, major associated with intrinsic acquired resistance anti-VEGF therapy discussed. The also describes from studies on novel non-VEGF several approaches normalization tumor vasculature by pericytes, utilization microRNAs extracellular tumor-associate vesicles, using immunotherapeutic drugs, nanotechnology.

Language: Английский

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Barriers to immune cell infiltration in tumors

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(4), P. e006401 - e006401

Published: April 1, 2023

Increased immune cell infiltration into tumors is associated with improved patient survival and predicts response to therapies. Thus, identification of factors that determine the extent crucial, so methods intervene on these targets can be developed. T cells enter tumor tissues through vasculature, under control interactions between homing receptors receptor ligands (HRLs) expressed by vascular endothelium nests. HRLs are often deficient in tumors, there also may active barriers infiltration. These remain understudied but crucial for enhancing immune-mediated cancer control. Multiple intratumoral systemic therapeutic approaches show promise enhance infiltration, including both approved therapies experimental This review highlights intracellular extracellular determinants intervention

Language: Английский

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Vascular Endothelial Growth Factor Ligands and Receptors in Breast Cancer

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(6), P. 2412 - 2412

Published: March 21, 2023

Breast cancer (BC) is the most common malignancy responsible for largest number of deaths in women worldwide. The risk developing BC predisposed by many factors such as age, presence genetic mutations or body weight. diagnosis mostly made relatively late, which why patients are exposed to radical surgical treatments, long-term chemotherapy and lower survival rates. There no sufficiently sensitive specific screening tests; therefore, researchers still looking new diagnostic biomarkers that would indicate appearance neoplastic changes initial stage neoplasm. VEGF family proteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D, EG-VEGF, PlGF) their receptors significant pathogenesis BC. They play a role process angiogenesis lymphangiogenesis both physiological pathological conditions. usefulness these potential has been initially proven. Moreover, blockage VEGF-related pathways seems be valid therapeutic target. Recent studies have tried describe novel strategies, including targeting pericytes, use miRNAs extracellular tumor-associated vesicles, immunotherapeutic drugs nanotechnology. This indicates possible contribution formation breast targets.

Language: Английский

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Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer

Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 1076 - 1076

Published: Feb. 29, 2024

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease effectiveness of treatment. They release chemokines cytokines from tumor microenvironment (TME). To improve treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems specific pathway-blocking agents using nanocarriers are a few them. This study explored nanocarrier roles strategies treatment profile’s by striving for TME. A biofunctionalized stimulates biosystem interaction, cellular uptake, immune system escape, vascular changes penetration into Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, immunity-modulating conjugated or modified co-administered condition-modulating can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation surface modification ligands enhance active targeting efficacy bypassing carrier inorganic organic compound complex-loaded drugs is convenient NSCLC-targeted therapy.

Language: Английский

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Normalization of tumor vasculature by imiquimod: proposal for a new anticancer therapeutic indication for a TLR7 agonist

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(3)

Published: Feb. 1, 2025

Imiquimod (IMQ), a drug from aminoquinoline group, is the toll-like receptor 7 (TLR7) agonist. It acts as an immunostimulant and radio-sensitizing agent. IMQ stimulates both innate adaptive immune response. Despite studies conducted, there are no unambiguous data showing how affects condition of tumor blood vessels. Tumor vasculature plays main role in progression. Formation abnormal vessels increases area hypoxia which recruits suppressor cells, blocks infiltration by CD8+ T lymphocytes, inhibits efficacy chemoterapeutic leads to cancer relapse. Normalization type therapy targeted at Here, we demonstrated that 50 µg growth melanoma tumors more efficiently, compared other tested doses control group. Dose escalation did not improve therapeutic antitumor potential TLR7 A dose most effectively reduced vessel density. normalized structurally (by reducing tortuosity increasing pericyte coverage) functionally improving perfusion) dose-dependent manner. Hypoxia regions treated mice were significantly after administration. had also greatest impact on changes tumor-infiltrating lymphocytes levels. agonist inhibited angiogenesis mice. Functional vascular normalization effectiveness low doxorubicin. Higher showed worse effects than lower including decreased perfusion, increased immunosuppression. This knowledge may help optimize combination selected with e.g. chemotherapy or radiotherapy elicit synergistic effect treatment. To conclude, outline repurposing normalizing Our research results contribute expanding indications for use anticancer future.

Language: Английский

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Extracellular Vesicles as Delivery Shippers for Noncoding RNA‐Based Modulation of Angiogenesis: Insights from Ischemic Stroke and Cancer

Small, Journal Year: 2023, Volume and Issue: 19(17)

Published: Jan. 2, 2023

Ischemic stroke and systemic cancer are two of the leading causes mortality. Hypoxia is a central pathophysiological component in ischemic cancer, representing joint medical function. This function includes angiogenesis regulation. Vascular remodeling coupled with axonal outgrowth following cerebral ischemia critical improving poststroke neurological functional recovery. Antiangiogenic strategies can inhibit vascularization play vital role impeding growth, invasion, metastasis. Although there significant differences cause across both conditions, emerging evidence states that common signaling structures, such as extracellular vesicles (EVs) noncoding RNAs (ncRNAs), involved this context. EVs, heterogeneous membrane encapsulating proteomic genetic information from parental cells, act multifunctional regulators intercellular communication. Among multifaceted roles modulating biological responses, exhaustive shows ncRNAs selectively sorted into specific aspects development prognosis, namely, angiogenesis. review will discuss recent advancements EV-facilitated/inhibited progression elements particular concern about within these vesicles. The concluded by underlining clinical opportunities EV-derived diagnostic, prognostic, therapeutic agents.

Language: Английский

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A gene for all seasons: The evolutionary consequences of HIF-1 in carcinogenesis, tumor growth and metastasis

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 102-103, P. 17 - 24

Published: July 1, 2024

Oxygen played a pivotal role in the evolution of multicellularity during Cambrian Explosion. Not surprisingly, responses to fluctuating oxygen concentrations are integral cancer—a disease characterized by breakdown multicellularity. Poorly organized tumor vasculature results chaotic patterns blood flow large spatial and temporal variations intra-tumoral concentrations. Hypoxia-inducible growth factor (HIF-1) plays enabling cells adapt, metabolize, proliferate low conditions. HIF-1 is often constitutively activated cancers, underscoring its importance cancer progression. Here, we argue that phenotypic changes mediated HIF-1, addition adapting their local environment, also "pre-adapt" them for proliferation at distant, metastatic sites. HIF-1-mediated adaptations include metabolic shift towards anaerobic respiration or glycolysis, activation cell survival mechanisms like plasticity epigenetic reprogramming, formation through angiogenesis. Hypoxia induced reprogramming can trigger epithelial mesenchymal transition cells—the first step cascade. Highly glycolytic facilitate invasion acidifying microenvironment. New vessels, formed due angiogenesis, provide conduit circulatory system. Moreover, acquired primary site allow remodel tissue generating promoting Thus, hypoxia promoted conducive all stages cascade from initial escape entry into vessel, intravascular survival, extravasation distant tissues, establishment secondary tumors.

Language: Английский

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