Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets

Seminars in Cancer Biology, Journal Year: 2019, Volume and Issue: 60, P. 14 - 27

Published: Aug. 14, 2019

Language: Английский

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Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy

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

Published: Aug. 28, 2019

Among all the stromal cells that present in tumor microenvironment, cancer-associated fibroblasts (CAFs) are one of most abundant and critical components mesenchyme, which not only provide physical support for but also play a key role promoting retarding tumorigenesis context-dependent manner. CAFs have been involved modulation many immune system, recent studies revealed their roles evasion poor responses to cancer immunotherapy. In this review, we describe our current understanding tumorigenic significance, origin, heterogeneity CAFs, as well different subtypes distinct cell types. More importantly, highlight potential therapeutic strategies target unleash system against tumor.

Language: Английский

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The matrix in cancer

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(4), P. 217 - 238

Published: Feb. 15, 2021

Language: Английский

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Defining the Hallmarks of Metastasis

Cancer Research, Journal Year: 2019, Volume and Issue: 79(12), P. 3011 - 3027

Published: May 3, 2019

Abstract Metastasis is the primary cause of cancer morbidity and mortality. The process involves a complex interplay between intrinsic tumor cell properties as well interactions cells multiple microenvironments. outcome development nearby or distant discontiguous secondary mass. To successfully disseminate, metastatic acquire in addition to those necessary become neoplastic. Heterogeneity mechanisms involved, routes dissemination, redundancy molecular pathways that can be utilized, ability piggyback on actions surrounding stromal makes defining hallmarks metastasis extraordinarily challenging. Nonetheless, this review identifies four distinguishing features are required: motility invasion, modulate site local microenvironments, plasticity, colonize tissues. By these first principles metastasis, we provide means for focusing efforts aspects will improve patient outcomes.

Language: Английский

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Metastasis Organotropism: Redefining the Congenial Soil

Developmental Cell, Journal Year: 2019, Volume and Issue: 49(3), P. 375 - 391

Published: May 1, 2019

Language: Английский

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Spatially confined sub-tumor microenvironments in pancreatic cancer

Cell, Journal Year: 2021, Volume and Issue: 184(22), P. 5577 - 5592.e18

Published: Oct. 1, 2021

Intratumoral heterogeneity is a critical frontier in understanding how the tumor microenvironment (TME) propels malignant progression. Here, we deconvolute human pancreatic TME through large-scale integration of histology-guided regional multiOMICs with clinical data and patient-derived preclinical models. We discover "subTMEs," histologically definable tissue states anchored fibroblast plasticity, relationships to immunity, subtypes, differentiation, treatment response. "Reactive" subTMEs rich complex but functionally coordinated communities were immune hot inhabited by aggressive cell phenotypes. The matrix-rich "deserted" harbored fewer activated fibroblasts tumor-suppressive features yet markedly chemoprotective enriched upon chemotherapy. SubTMEs originated differentiation trajectories, transitory notable both single-cell transcriptomics situ. intratumoral co-occurrence produced patient-specific phenotypic computationally predictable tightly linked biology. Therefore, within plentiful, notorious not random marks fundamental organizational units.

Language: Английский

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Extracellular vesicles as tools and targets in therapy for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 5, 2024

Abstract Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers ubiquitously released from cells under normal pathological conditions. Human serum is a rich source of these EVs, though their isolation proteins non-EV lipid particles poses challenges. These transport various cellular components such as proteins, mRNAs, miRNAs, DNA, lipids across distances, influencing numerous physiological events, including those within tumor microenvironment (TME). Their pivotal roles in communication make EVs promising candidates for therapeutic agents, drug delivery systems, disease biomarkers. Especially cancer diagnostics, EV detection can pave way early identification offers potential diagnostic Moreover, subtypes emerging targeted tools, highlighting clinical significance. The need non-invasive biomarkers to monitor biological processes purposes remains unfulfilled. Tapping unique composition could unlock advanced avenues future. In this review, we discuss detail conditions, cancers (encompassing head neck, lung, gastric, breast, hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune renal diseases, emphasizing advancements molecular diagnostics delivery.

Language: Английский

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Crosstalk Between the MSI Status and Tumor Microenvironment in Colorectal Cancer

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 12, 2020

Colorectal cancer(CRC) patients have derived clinical benefits from immunotherapy, especially CRC with mismatch repair deficiency (dMMR)/microsatellite instability-high(MSI-H), whose sensitivity to immune checkpoint inhibitors(ICIs) is significantly higher than that of microsatellite-stable(MSS)/microsatellite instability-low(MSI-L). Most studies not systematically evaluated the characteristics and microenvironments MSI-H MSS/MSI-L CRC. We analyzed relationship between MSI status prognosis ICIs treatment in an immunotherapy cohort. further used mutation data for The Cancer Genome Atlas(TCGA)-CRC[Colon adenocarcinoma(COAD)+rectum adenocarcinoma(READ)] cohorts. For mRNA expression, analysis microenvironment immunogenicity under different was performed. Compared CRC, benefited treatment. found had more cell infiltration, expression immune-related genes MSS/MSI-L. MANTIS score predict positively correlated cells, genes, immunogenicity. In addition, subtype showed COAD READ might microenvironments. may inflammatory tumor increased ICIs. Unlike those READ, be consistent

Language: Английский

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Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: June 3, 2022

Hypoxia, a common feature of the tumor microenvironment in various types cancers, weakens cytotoxic T cell function and causes recruitment regulatory cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia hypoxia-inducible factors (HIFs) 1 2 alpha (HIF1A HIF2A) are involved immune escape. Under hypoxia, activation HIF1A induces series signaling events, including through programmed death receptor-1/programmed ligand-1. Moreover, triggers shedding complex class I chain-associated molecules nitric oxide impairment to disrupt surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances escape via increased cell-platelet binding. HIF2A upregulates stem factor expression recruit tumor-infiltrating mast cells increase levels cytokines interleukin-10 transforming growth factor-β, resulting an immunosuppressive microenvironment. Additionally, tumor-associated long noncoding RNAs suppresses function, enabling Overall, elucidating underlying mechanisms which HIFs promote evasion will allow for targeting HIF treatment. This review discusses current knowledge how facilitate escape, with evidence date implicating as molecular target such provides further insight into mechanism strategies immunotherapy suggested.

Language: Английский

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Metastasis-Initiating Cells and Ecosystems

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 971 - 994

Published: April 1, 2021

Abstract Metastasis is initiated and sustained through therapy by cancer cells with stem-like immune-evasive properties, termed metastasis-initiating (MIC). Recent progress suggests that MICs result from the adoption of a normal regenerative progenitor phenotype malignant cells, intrinsic programs to survive stresses metastatic process, undergo epithelial–mesenchymal transitions, enter slow-cycling states for dormancy, evade immune surveillance, establish supportive interactions organ-specific niches, co-opt systemic factors growth recurrence after therapy. Mechanistic understanding molecular mediators MIC phenotypes host tissue ecosystems could yield therapeutics improve patient outcomes. Significance: Understanding origins, traits, vulnerabilities capacity initiate metastasis in distant organs, microenvironments support ability these surveillance regenerate tumor, critical developing strategies prevention treatment advanced cancer. Leveraging recent our here we review nature their offer perspective on how this knowledge informing innovative treatments cancers.

Language: Английский

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