The Tumor Microenvironment Innately Modulates Cancer Progression

Cancer Research, Journal Year: 2019, Volume and Issue: 79(18), P. 4557 - 4566

Published: July 26, 2019

Cancer development and progression occurs in concert with alterations the surrounding stroma. cells can functionally sculpt their microenvironment through secretion of various cytokines, chemokines, other factors. This results a reprogramming cells, enabling them to play determinative role tumor survival progression. Immune are important constituents stroma critically take part this process. Growing evidence suggests that innate immune (macrophages, neutrophils, dendritic lymphoid myeloid-derived suppressor natural killer cells) as well adaptive (T B contribute when present (TME). Cross-talk between cancer proximal ultimately an environment fosters growth metastasis. Understanding nature dialog will allow for improved therapeutics simultaneously target multiple components TME, increasing likelihood favorable patient outcomes.

Language: Английский

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Metabolism of immune cells in cancer

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(9), P. 516 - 531

Published: July 6, 2020

Language: Английский

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Role of Glutathione in Cancer: From Mechanisms to Therapies

Biomolecules, Journal Year: 2020, Volume and Issue: 10(10), P. 1429 - 1429

Published: Oct. 9, 2020

Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, xenobiotics. Recent studies have highlighted importance GSH key signal transduction reactions controller cell differentiation, proliferation, apoptosis, ferroptosis immune function. Molecular changes antioxidant system disturbances homeostasis been implicated tumor initiation, progression, treatment response. Hence, has both protective pathogenic roles. Although healthy crucial for removal detoxification carcinogens, elevated levels are associated with progression increased resistance to chemotherapeutic drugs. Recently, several novel therapies developed target tumors means response decreased drug resistance. In this comprehensive review we explore mechanisms functionalities different therapeutic approaches that either directly, indirectly or use GSH-based prodrugs. Consideration also given computational methods used describe related processes silico testing effects.

Language: Английский

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In search of definitions: Cancer‐associated fibroblasts and their markers

International Journal of Cancer, Journal Year: 2019, Volume and Issue: 146(4), P. 895 - 905

Published: Feb. 8, 2019

The tumor microenvironment has been identified as one of the driving factors progression and invasion. Inside this microenvironment, cancer-associated fibroblasts (CAFs), a type perpetually activated fibroblasts, have implicated to strong tumor-modulating effect play key role in areas such drug resistance. Identification CAFs typically carried based on expression various "CAF markers", fibroblast activation protein alpha (FAP) smooth muscle actin (αSMA), which separates them from larger pool present body. However, outlined Review, commonly used markers is extremely heterogeneous varies strongly between different CAF subpopulations. As such, novel selection methods cellular function, well further characterizing research, are vital for standardization identification order improve cross-applicability research studies field. aim review give thorough overview field their strengths and, more importantly, weaknesses, highlight potential future avenues targeting.

Language: Английский

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Conquering the Hypoxia Limitation for Photodynamic Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(48)

Published: Sept. 27, 2021

Photodynamic therapy (PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due the hypoxic nature characteristic of many solid tumors, PDT is frequently limited therapeutic effect. Moreover, consumption O2 during may further aggravate tumor condition, which promotes proliferation, metastasis, invasion resulting poor prognosis treatment. Therefore, numerous efforts have been made increase content with goal enhancing efficacy. Herein, these strategies developed past decade are comprehensively reviewed alleviate hypoxia, including 1) delivering exogenous directly, 2) generating situ, 3) reducing cellular by inhibiting respiration, 4) regulating TME, (e.g., normalizing vasculature or disrupting extracellular matrix), 5) hypoxia-inducible factor 1 (HIF-1) signaling pathway relieve hypoxia. Additionally, -independent Type-I also discussed as an alternative strategy. By reviewing progress, it hoped that this review will provide innovative perspectives new nanomaterials designed combat hypoxia avoid associated limitation PDT.

Language: Английский

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Clinical update on head and neck cancer: molecular biology and ongoing challenges

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(8)

Published: July 15, 2019

Abstract Head and neck squamous cell carcinomas (HNSCCs) are an aggressive, genetically complex difficult to treat group of cancers. In lieu truly effective targeted therapies, surgery radiotherapy represent the primary treatment options for most patients. But these treatments associated with significant morbidity a reduction in quality life. Resistance both only available therapy, subsequent relapse common. Research has therefore focussed on identifying biomarkers stratify patients into clinically meaningful groups develop more therapies. However, as we now discovering, poor response therapy aggressive nature HNSCCs is not affected by alterations intracellular signalling pathways but also heavily influenced behaviour extracellular microenvironment. The HNSCC tumour landscape environment permissive tumours’ nature, fostered actions immune system, hypoxia influence microbiome. Solving challenges rests expanding our knowledge areas, parallel greater understanding molecular biology subtypes. This update aims build earlier 2014 review bringing up date provide insights areas ongoing research perspectives future.

Language: Английский

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Tumor microenvironment: Challenges and opportunities in targeting metastasis of triple negative breast cancer

Pharmacological Research, Journal Year: 2020, Volume and Issue: 153, P. 104683 - 104683

Published: Feb. 9, 2020

Language: Английский

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Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: March 30, 2019

The tumor microenvironment represents a complex network, in which cells not only communicate with each other but also stromal and immune cells. Current research has demonstrated the vital role of supporting phenotype via sophisticated system intercellular communication through direct cell-to-cell contact or by classical paracrine signaling loops cytokines growth factors. Recently, extracellular vesicles have emerged as an important mechanism cellular interchange bioactive molecules. Extracellular isolated from been implicated various steps progression, such proliferation, angiogenesis, metastasis, drug resistance. Inhibition secretion, thus transfer oncogenic molecules, holds promise for preventing This review focuses on modulating addressing different aspects bidirectional interactions among tumor-associated contribution to resistance will be discussed well therapeutic strategies targeting production treatment cancer.

Language: Английский

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p53 signaling in cancer progression and therapy

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: Dec. 1, 2021

Abstract The p53 protein is a transcription factor known as the "guardian of genome" because its critical function in preserving genomic integrity. TP53 gene mutated approximately half all human malignancies, including those breast, colon, lung, liver, prostate, bladder, and skin. When DNA damage occurs, on chromosome 17 stops cell cycle. If mutated, cycle unrestricted damaged replicated, resulting uncontrolled proliferation cancer tumours. Tumor-associated mutations are usually associated with phenotypes distinct from caused by loss tumor-suppressing exerted wild-type p53protein. Many these mutant proteins have oncogenic characteristics, therefore modulate ability cells to proliferate, escape apoptosis, invade metastasize. Because deficiency so common cancer, this an excellent option for treatment. In review, we will discuss some molecular pathways which might perform their activities, well prospective treatment methods based restoring tumor suppressive functions.

Language: Английский

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Proteogenomic characterization of pancreatic ductal adenocarcinoma

Cell, Journal Year: 2021, Volume and Issue: 184(19), P. 5031 - 5052.e26

Published: Sept. 1, 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 tissues. Proteomic, phosphoproteomic, glycoproteomic analyses were used to characterize proteins their modifications. In addition, whole-genome sequencing, whole-exome methylation, RNA sequencing (RNA-seq), microRNA (miRNA-seq) performed on same tissues facilitate an integrated determine impact genomic protein expression, signaling pathways, post-translational To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using features verified pathological estimation based histological review. This characterization will serve as valuable resource for community, paving way early detection identification novel therapeutic targets.

Language: Английский

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