The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth

Cancer Cell, Год журнала: 2023, Номер 41(3), С. 374 - 403

Опубликована: Март 1, 2023

Язык: Английский

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Angiogenic signaling pathways and anti-angiogenic therapy for cancer

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 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

Язык: Английский

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The role of microenvironment in tumor angiogenesis

Journal of Experimental & Clinical Cancer Research, Год журнала: 2020, Номер 39(1)

Опубликована: Сен. 30, 2020

Abstract Tumor angiogenesis is necessary for the continued survival and development of tumor cells, plays an important role in their growth, invasion, metastasis. The microenvironment—composed surrounding secreted cytokines—provides a conducive environment growth tumors. Different components microenvironment can regulate development. In this review, we have discussed regulatory angiogenesis. High expression angiogenic factors inflammatory cytokines microenvironment, as well hypoxia, are presumed to be reasons poor therapeutic efficacy current anti-angiogenic drugs. A combination drugs antitumor or hypoxia inhibitors might improve outcome.

Язык: Английский

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Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity

Experimental & Molecular Medicine, Год журнала: 2020, Номер 52(9), С. 1475 - 1485

Опубликована: Сен. 1, 2020

Abstract Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced cancers. However, tumor microenvironment (TME) functions as a formidable barrier that severely impairs efficacy ICIs. While crosstalk between vessels and cells determines nature anti-tumor immunity, it is skewed toward destructive cycle in growing tumors. First, disorganized hinder CD8 + T cell trafficking into TME, disable effector functions, even kill cells. Moreover, VEGF, key driver angiogenesis, interferes maturation dendritic cells, thereby suppressing priming, VEGF also induces TOX-mediated exhaustion Meanwhile, variety innate adaptive contribute to malformation vessels. Protumoral M2-like macrophages well H 2 Treg secrete pro-angiogenic factors accelerate uncontrolled angiogenesis promote vascular immaturity. CD4 1 suppress induce by secreting IFN-γ, they are unable infiltrate TME due malformed These findings led preclinical studies demonstrated simultaneous targeting immunity viable strategy normalize aberrant vascular-immune potentiate cancer immunotherapy. Furthermore, this combination been evidently through recent pivotal clinical trials, granted approval from FDA, now being used patients kidney, liver, lung, or uterine cancer. Overall, combining anti-angiogenic therapy ICI valid therapeutic can enhance will further expand landscape treatment.

Язык: Английский

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PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Март 24, 2022

Cancer is a severe public health issue that leading cause of mortality globally. It also an impediment to improving life expectancy worldwide. Furthermore, the global burden cancer incidence and death continuously growing. Current therapeutic options are insufficient for patients, tumor complexity heterogeneity necessitate customized medicine or targeted therapy. critical identify potential targets. Aberrant activation PI3K/AKT/mTOR pathway has significant role in carcinogenesis. This review summarized oncogenic PI3K/Akt/mTOR alterations various hallmarks associated with pathway, such as cell proliferation, autophagy, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT), chemoresistance. Importantly, this provided recent advances inhibitor research. Overall, in-depth understanding association between tumorigenesis development therapies targeting will help make clinical decisions.

Язык: Английский

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NF-κB: At the Borders of Autoimmunity and Inflammation

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Авг. 9, 2021

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions serves as a pivotal mediator inflammatory response. In the first part this review, we discuss inducers, signaling pathways, regulators involved in homeostasis well detail importance post-translational regulation by ubiquitination function. We also indicate stages central peripheral tolerance where plays fundamental role. With respect to tolerance, how medullary thymic epithelial cell (mTEC) development, homeostasis, Moreover, elaborate on its role migration double-positive (DP) thymocytes from cortex medulla. outline contributes inactivation destruction autoreactive T B lymphocytes differentiation CD4+-T subsets that are implicated tolerance. latter half describe contribution pathogenesis autoimmunity autoinflammation. recent discovery mutations involving components pathway has both deepened our understanding autoimmune disease informed new therapeutic approaches treat these illnesses.

Язык: Английский

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Molecular Bases of VEGFR-2-Mediated Physiological Function and Pathological Role

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Ноя. 16, 2020

The VEGF/VEGFR-2 system participates in vasculogenesi and angiogenesis. Angiogenesis, as an important mechanism many physiological pathological processes, is involved endothelial cell proliferation, migration, survival, leads to further tubulogenesis, finally promotes formation of vessels. This series signaling cascade pathways are precisely mediated by system. VEGF binding the IgD2 IgD3 VEGFR-2 induces dimerization receptor, subsequently activation trans-autophosphorylation tyrosine kinase, then initiation intracellular cascades, VEGF-activated stimulates mediates variety transduction, biological responses, processes angiogenesis, which several crucial phosphorylated sites Tyr801, Try951, Try1175, Try1214 domains mediate key including PLCγ-PKC, TSAd-Src-PI3K-Akt, SHB-FAK-paxillin, SHB-PI3K-Akt, NCK-p38-MAPKAPK2/3 pathways. Based on molecular structure VEGFR-2, strategy VEGFR-2-targeted therapy should be considered employ treatment this system-associated diseases blocking pathway, inhibiting gene expression, destroying vascular cells expressing VEGFR-2.

Язык: Английский

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Resistance Mechanisms to Anti-angiogenic Therapies in Cancer

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Фев. 27, 2020

Tumor growth and metastasis rely on tumor vascular network for the adequate supply of oxygen nutrients. angiogenesis relies a highly complex program factor signaling, endothelial cell (EC) proliferation, extracellular matrix (ECM) remodeling, stromal interactions. Numerous pro-angiogenic drivers have been identified, most important which is (VEGF). The importance inducers in growth, invasion extravasation make them an excellent therapeutic target several types cancers. Hence, number anti-angiogenic agents developed cancer treatment has risen over past decade, with at least eighty drugs being investigated preclinical studies phase I-III clinical trials. To date, common approaches to inhibition VEGF axis include blockade receptors (VEGFRs) or ligands by neutralizing antibodies, as well receptor tyrosine kinase (RTK) enzymes. Despite promising results, monotherapies led only mild benefits. minimal benefits could be secondary primary acquired resistance, through activation alternative mechanisms that sustain vascularization growth. Mechanisms resistance are categorized into VEGF-dependent alterations, non-VEGF pathways Thus, complementary such combination these inhibitors targeting blood vessel formation urgently needed. This review provides updated overview pathophysiology during It also sheds light different date. Finally, it highlights evidence angiogenic suggests novel might exploited ultimate aim overcoming improving outcomes patients cancer.

Язык: Английский

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The Role of Macrophages in Cancer Development and Therapy

Cancers, Год журнала: 2021, Номер 13(8), С. 1946 - 1946

Опубликована: Апрель 18, 2021

Macrophages are critical mediators of tissue homeostasis and influence various aspects immunity. Tumor-associated macrophages one the main cellular components tumor microenvironment. Depending on their activation status, can exert a dual tumorigenesis by either antagonizing cytotoxic activity immune cells or, less frequently, enhancing antitumor responses. In most situations, TAMs suppress T cell recruitment function or regulate other The importance targeting in cancer therapy is derived from strong association between high infiltration with poor patient prognosis. Several macrophage-targeting approaches anticancer developed, including TAM depletion, inhibition new differentiation, re-education for phagocytosis. this review, we will describe role development, such as protumorigenic inflammation, suppression, neoangiogenesis, enhancement invasion distant metastasis. Furthermore, discuss therapeutic that aim to deplete contrary, re-educate phagocytosis

Язык: Английский

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Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours

Nature, Год журнала: 2023, Номер 618(7965), С. 598 - 606

Опубликована: Май 31, 2023

Язык: Английский

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