VEGF in Signaling and Disease: Beyond Discovery and Development

Cell, Journal Year: 2019, Volume and Issue: 176(6), P. 1248 - 1264

Published: March 1, 2019

Language: Английский

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Tumor angiogenesis: causes, consequences, challenges and opportunities

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 77(9), P. 1745 - 1770

Published: Nov. 6, 2019

Abstract Tumor vascularization occurs through several distinct biological processes, which not only vary between tumor type and anatomic location, but also occur simultaneously within the same cancer tissue. These processes are orchestrated by a range of secreted factors signaling pathways can involve participation non-endothelial cells, such as progenitors or stem cells. Anti-angiogenic therapies using either antibodies tyrosine kinase inhibitors have been approved to treat types cancer. However, benefit treatment has so far modest, some patients responding at all others acquiring resistance. It is becoming increasingly clear that blocking tumors from accessing circulation an easy task accomplish. vessel functionality gene expression often differ vastly when comparing different subtypes, phenotype be markedly heterogeneous single tumor. Here, we summarize current understanding cellular molecular mechanisms involved in angiogenesis discuss challenges opportunities associated with vascular targeting.

Language: Английский

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Comprehensive review of targeted therapy for colorectal cancer

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: March 20, 2020

Abstract Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in world was responsible for nearly 881,000 cancer-related deaths 2018. Surgery chemotherapy have long been first choices patients. However, prognosis of CRC has never satisfying, especially patients with metastatic lesions. Targeted therapy a new optional approach that successfully prolonged overall survival Following successes anti-EGFR (epidermal growth factor receptor) agent cetuximab anti-angiogenesis bevacizumab, agents blocking different critical pathways as well immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide currently updating recommended targeted drugs on basis increasing number high-quality clinical trials. This review provides overview existing CRC-targeted their underlying mechanisms, discussion limitations future trends.

Language: Английский

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Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(2), P. 190 - 202

Published: Dec. 18, 2018

Language: Английский

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The obese adipose tissue microenvironment in cancer development and progression

Nature Reviews Endocrinology, Journal Year: 2018, Volume and Issue: 15(3), P. 139 - 154

Published: Nov. 20, 2018

Language: Английский

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Normalizing Function of Tumor Vessels: Progress, Opportunities, and Challenges

Annual Review of Physiology, Journal Year: 2019, Volume and Issue: 81(1), P. 505 - 534

Published: Feb. 10, 2019

Abnormal blood and lymphatic vessels create a hostile tumor microenvironment characterized by hypoxia, low pH, elevated interstitial fluid pressure. These abnormalities fuel progression, immunosuppression, treatment resistance. In 2001, we proposed novel hypothesis that the judicious use of antiangiogenesis agents—originally developed to starve tumors—could transiently normalize improve outcome anticancer drugs administered during window normalization. addition providing preclinical clinical evidence in support this hypothesis, also revealed underlying molecular mechanisms. parallel, demonstrated desmoplasia could impair vascular function compressing vessels, normalizing extracellular matrix both settings. Here, summarize progress made understanding applying normalization concept cancer outline opportunities challenges ahead patient outcomes using various strategies.

Language: Английский

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Adipocyte and lipid metabolism in cancer drug resistance

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(8), P. 3006 - 3017

Published: July 1, 2019

Development of novel and effective therapeutics for treating various cancers is probably the most congested challenging enterprise pharmaceutical companies. Diverse drugs targeting malignant nonmalignant cells receive clinical approval each year from FDA. Targeting cancer unavoidably changes tumor microenvironment, cellular molecular components relentlessly alter in response to drugs. Cancer often reprogram their metabolic pathways adapt environmental challenges facilitate survival, proliferation, metastasis. While cells' dependence on glycolysis energy production well studied, roles adipocytes lipid reprogramming supporting growth, metastasis, drug responses are less understood. This Review focuses emerging mechanisms involving metabolism altering treatment. In particular, we discuss underlying cancer-associated resistance.

Language: Английский

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Cancer-associated adipocytes: key players in breast cancer progression

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Sept. 9, 2019

Adipocytes are one of the primary stromal cells in many tissues, and they considered to play an active role tumor microenvironment. Cancer-associated adipocytes (CAAs) not only found adjacent cancer cells, but also communicate with through releasing various factors that can mediate local systemic effects. The adipocyte-cancer cell crosstalk leads phenotypical functional changes both types, which further enhance progression. Indeed, obesity, is associated increase adipose mass alteration tissue, becoming pandemic some countries it now be independent risk factor for In this review, we focus on potential mechanisms involved special attention circle breast cancer. We envisage besides having a direct impact CAAs systemically preconditions microenvironment by favoring anti-tumor immunity. A better understanding cancer-associated key molecular events will provide insights into biology permit optimization therapeutic strategies.

Language: Английский

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Aspects of the Tumor Microenvironment Involved in Immune Resistance and Drug Resistance

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: May 27, 2021

The tumor microenvironment (TME) is a complex and ever-changing “rogue organ” composed of its own blood supply, lymphatic nervous systems, stroma, immune cells extracellular matrix (ECM). These components, utilizing both benign malignant cells, nurture the harsh, immunosuppressive nutrient-deficient environment necessary for cell growth, proliferation phenotypic flexibility variation. An important aspect TME cellular crosstalk cell-to-ECM communication. This interaction induces release soluble factors responsible evasion ECM remodeling, which further contribute to therapy resistance. Other aspects are presence exosomes contributed by circulating deregulated microRNAs TME-specific metabolic patterns potentiate progression and/or resistance therapy. In addition biochemical signaling, specific characteristics such as hypoxic environment, derangements, abnormal mechanical forces have been implicated in development treatment this review, we will provide an overview microenvironmental composition, structure, features that influence suppression

Language: Английский

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HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(10), P. 5074 - 5087

Published: Sept. 1, 2020

Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis metabolic rewiring are well-established drivers of breast aggressiveness, therapy resistance, poor prognosis. Targeting HIF its downstream targets in metabolism has been unsuccessful so far clinical setting, with major unresolved challenges residing target selection, development robust biomarkers for response prediction, understanding harnessing escape mechanisms. This Review discusses pathophysiological role HIFs, angiogenesis, targeting these features patients cancer. Rational therapeutic combinations, especially immunotherapy endocrine therapy, seem most promising exploitation intricate interplay cells tumor microenvironment.

Language: Английский

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