The CCL5/CCR5 Axis in Cancer Progression

Cancers, Год журнала: 2020, Номер 12(7), С. 1765 - 1765

Опубликована: Июль 2, 2020

Tumor cells can “hijack” chemokine networks to support tumor progression. In this context, the C-C ligand 5/C-C receptor type 5 (CCL5/CCR5) axis is gaining increasing attention, since abnormal expression and activity of CCL5 its CCR5 have been found in hematological malignancies solid tumors. Numerous preclinical vitro vivo studies shown a key role CCL5/CCR5 cancer, thus provided rationale for clinical trials using repurposed drug maraviroc, antagonist used treat HIV/AIDS. This review summarizes current knowledge on cancer. First, it describes involvement cancer progression, including autocrine paracrine growth, ECM (extracellular matrix) remodeling migration, stem cell expansion, DNA damage repair, metabolic reprogramming, angiogenesis. Then, focuses individual tumors which studied preclinically. Finally, discusses strategies counteract different cancers maraviroc or therapeutic monoclonal antibodies.

Язык: Английский

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Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(19), С. 10701 - 10701

Опубликована: Окт. 2, 2021

Chronic (continuous, non-interrupted) hypoxia and cycling (intermittent, transient) are two types of occurring in malignant tumors. They both associated with the activation hypoxia-inducible factor-1 (HIF-1) nuclear factor κB (NF-κB), which induce changes gene expression. This paper discusses detail mechanisms these transcription factors chronic crosstalk between signaling pathways. In particular, it focuses on importance reactive oxygen species (ROS), nitrogen (RNS) together nitric oxide synthase, acetylation HIF-1, action MAPK cascades. The also formation low-grade inflammation cancerous Finally, we discuss effects tumor microenvironment, particular expression VEGF-A, CCL2/MCP-1, CXCL1/GRO-α, CXCL8/IL-8, COX-2 PGE2. These angiogenesis recruit various cells into niche, including neutrophils monocytes which, tumor, transformed tumor-associated (TAN) macrophages (TAM) that participate tumorigenesis.

Язык: Английский

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Role of the CCL2‐CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting

Cell Proliferation, Год журнала: 2021, Номер 54(10)

Опубликована: Авг. 31, 2021

The chemokine ligand CCL2 and its receptor CCR2 are implicated in the initiation progression of various cancers. can activate tumour cell growth proliferation through a variety mechanisms. By interacting with CCR2, promotes cancer migration recruits immunosuppressive cells to microenvironment, favouring development. Over last several decades, series studies have been conducted explore CCL2-CCR2 signalling axis function malignancies. Therapeutic strategies targeting CCL2- also shown promising effects, enriching our approaches for fighting against cancer. In this review, we summarize role tumorigenesis highlight recent on targeted therapy, focusing preclinical clinical trials.

Язык: Английский

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Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook

Molecular Cancer, Год журнала: 2020, Номер 19(1)

Опубликована: Сен. 11, 2020

Abstract Immunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging overall survival (OS) advanced stage patients. Over recent years IO been broadly integrated into first-line setting non-oncogene driven NSCLC, either in combination with chemotherapy, or selected patients PD-L1 high expression as monotherapy. Still, a significant proportion suffer from disease progression. A better understanding resistance mechanisms depicts central goal to avoid overcome and improve patient outcome. We here review major cellular molecular pathways within tumor microenvironment (TME) that may impact evolution resistance. summarize upcoming treatment options after including novel targets (e.g. RIG-I, STING) well interesting combinational approaches such combined anti-angiogenic agents metabolic IDO-1, adenosine signaling, arginase). By discussing fundamental mode action TME, we aim understand manage seed new ideas for effective therapeutic concepts.

Язык: Английский

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The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(2), С. 843 - 843

Опубликована: Янв. 15, 2021

Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with hypoxia showing stronger proinflammatory influence. One systems affected CXC chemokine system. This paper reviews all available information hypoxia-induced changes in expression chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) well receptors-CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 CXCR8. First, we present basic these chemoattractant cytokines processes. We then discuss angiogenesis, lymphangiogenesis recruitment various cells to niche, including myeloid-derived suppressor (MDSCs), tumor-associated macrophages (TAMs), neutrophils (TANs), regulatory T (Tregs) tumor-infiltrating lymphocytes (TILs). Finally, review summarizes data use drugs targeting system therapies.

Язык: Английский

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Chemokine-Directed Tumor Microenvironment Modulation in Cancer Immunotherapy

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(18), С. 9804 - 9804

Опубликована: Сен. 10, 2021

Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have pivotal role in the migration pattern cells into tumor, thereby shaping tumor microenvironment profile, often towards pro-tumorigenic state. Furthermore, chemokines can directly target non-immune microenvironment, including stromal and vascular endothelial cells. As such, participate several cancer development processes such as angiogenesis, metastasis, proliferation, stemness invasiveness, therefore key determinants disease progression, with strong influence patient prognosis response to therapy. Due their multifaceted biology, chemokine network has emerged potential immunotherapy target. Under present review, we provide general overview effects on tumoral processes, well description currently available chemokine-directed therapies, highlighting both monotherapy or combination standard chemotherapy other immunotherapies. Finally, discuss most critical challenges prospects developing targeted therapeutic options.

Язык: Английский

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MLKL in cancer: more than a necroptosis regulator

Cell Death and Differentiation, Год журнала: 2021, Номер 28(6), С. 1757 - 1772

Опубликована: Май 5, 2021

Язык: Английский

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The Role of CXCL16 in the Pathogenesis of Cancer and Other Diseases

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(7), С. 3490 - 3490

Опубликована: Март 28, 2021

CXCL16 is a chemotactic cytokine belonging to the α-chemokine subfamily. It plays significant role in progression of cancer, as well course atherosclerosis, renal fibrosis, and non-alcoholic fatty liver disease (NAFLD). Since there has been no review paper discussing importance this chemokine various diseases, we have collected all available knowledge about review. In first part paper, discuss background information its receptor, CXCR6. Next, focus on variety with an emphasis cancer. We tumor cell proliferation, migration, invasion, metastasis. describe microenvironment, including involvement angiogenesis, significance tumor-associated cells (cancer associated fibroblasts (CAF), microglia, macrophages (TAM), neutrophils (TAN), mesenchymal stem (MSC), myeloid suppressor (MDSC), regulatory T (Treg)). Finally, antitumor properties CXCL16, which are mainly caused by natural killer (NKT) cells. At end article, summarize cancer therapy.

Язык: Английский

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The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited

Cancers, Год журнала: 2023, Номер 15(2), С. 376 - 376

Опубликована: Янв. 6, 2023

Tumorigenesis is a complex and dynamic process involving cell-cell cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance metastasis. This review provides an updated summary of the role played by microenvironment (TME) components hypoxia in tumorigenesis, highlight various ways through which cells reprogram normal into phenotypes are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages -endothelial cells. Tumor secrete numerous factors leading to transformation previously anti-tumorigenic environment pro-tumorigenic environment. Once formed, solid tumors continue interact with stromal cells, local infiltrating macrophages, mesenchymal stem endothelial pericytes, secreted ECM within (TME). The TME key response treatment outcome. Importantly, can initially be anti-tumorigenic, but over time promote tumorigenesis induce therapy resistance. To counter hypoxia, increased angiogenesis leads formation new vascular networks order actively sustain growth via supply oxygen nutrients, whilst removing metabolic waste. Angiogenic network aid metastatic dissemination. Successful novel development require identification therapeutic targeting cancer-associated- fibroblasts (CAFs) (CAMs), blocking ECM-receptor interactions, addition reprogramming immune success. Lastly, this highlights potential TME- hypoxia-centered therapies under investigation.

Язык: Английский

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Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain

Cancers, Год журнала: 2022, Номер 14(24), С. 6054 - 6054

Опубликована: Дек. 8, 2022

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the of many genes are responsible for adaptation and survival tumor cells in hypoxic environments. Over past few decades, tremendous efforts have been made to comprehensively understand role HIF-1 progression. Based on pivotal roles biology, inhibitors interrupting expression, stabilization, DNA binding properties, or transcriptional activity identified as potential therapeutic agents various cancers, yet none these successfully translated into clinically available cancer treatments. In this review, we briefly introduce regulation pathway summarize its cell proliferation, angiogenesis, metastasis. addition, explore implications development drug resistance cancer-related pain: most commonly encountered obstacles during conventional anticancer therapies. Finally, current status clinical trials their perspectives highlighted, along with modes action. This review provides new insights novel targeting HIF-1. may be promising combinational interventions improve efficacy treatments reduce pain.

Язык: Английский

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