Hallmarks of Cancer: New Dimensions

Cancer Discovery, Journal Year: 2022, Volume and Issue: 12(1), P. 31 - 46

Published: Jan. 1, 2022

The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity phenotypes and genotypes into provisional set underlying principles. As knowledge mechanisms has progressed, other facets disease have emerged as potential refinements. Herein, prospect raised that phenotypic plasticity disrupted differentiation discrete hallmark capability, nonmutational epigenetic reprogramming polymorphic microbiomes both constitute distinctive enabling characteristics facilitate acquisition capabilities. Additionally, senescent cells, varying origins, may be added to roster functionally important cell types in tumor microenvironment. SIGNIFICANCE: Cancer daunting breadth scope its diversity, spanning genetics, tissue biology, pathology, response therapy. Ever more powerful experimental computational tools technologies are providing an avalanche "big data" about myriad manifestations diseases encompasses. integrative concept embodied helping distill this increasingly logical science, new dimensions presented perspective add value endeavor, fully understand development malignant progression, apply medicine.

Language: Английский

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Hallmarks of aging: An expanding universe

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 243 - 278

Published: Jan. 1, 2023

Language: Английский

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Cellular senescence in ageing: from mechanisms to therapeutic opportunities

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(2), P. 75 - 95

Published: Dec. 16, 2020

Language: Английский

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Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 29, 2021

Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells response to various intrinsic and extrinsic stimuli, as well developmental signals. Senescence considered highly dynamic, multi-step process, during which the properties of senescent continuously evolve diversify context dependent manner. It associated with multiple cellular molecular changes distinct phenotypic alterations, including proliferation unresponsive mitogenic stimuli. Senescent remain viable, have alterations metabolic activity undergo dramatic gene expression develop complex senescence-associated secretory phenotype. compromise tissue repair regeneration, thereby contributing toward aging. Removal attenuate age-related dysfunction extend health span. also act potent anti-tumor mechanism, by preventing potentially cancerous cells. program acts double-edged sword, both beneficial detrimental effects on organism, an example evolutionary antagonistic pleiotropy. Activation p53/p21 WAF1/CIP1 p16 INK4A /pRB tumor suppressor pathways play central role regulating senescence. Several other recently been implicated mediating Herein we review mechanisms underlie growth particular focus why stop dividing, stability arrest, hypersecretory phenotype how different are all integrated.

Language: Английский

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Diversity and Biology of Cancer-Associated Fibroblasts

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(1), P. 147 - 176

Published: May 29, 2020

Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite presence of non-neoplastic stromal components that substantially contribute progression tumor. Indeed, cancer cell survival, growth, migration, and even dormancy are influenced by surrounding tumor microenvironment (TME). Within TME, cancer-associated fibroblasts (CAFs) been shown play several roles in development a They secrete growth factors, inflammatory ligands, extracellular matrix proteins promote proliferation, therapy resistance, immune exclusion. However, recent work indicates CAFs may also restrain some circumstances. In this review, we summarize body CAFs, with particular focus most discoveries about fibroblast heterogeneity, plasticity, functions. We highlight commonalities present across different types, normal states. Finally, latest advances regarding therapeutic strategies undergoing preclinical clinical evaluation.

Language: Английский

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Cellular senescence and senolytics: the path to the clinic

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(8), P. 1556 - 1568

Published: Aug. 1, 2022

Language: Английский

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How the ageing microenvironment influences tumour progression

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 20(2), P. 89 - 106

Published: Dec. 13, 2019

Language: Английский

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Exploiting senescence for the treatment of cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(6), P. 340 - 355

Published: March 3, 2022

Language: Английский

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A guide to assessing cellular senescencein vitroandin vivo

FEBS Journal, Journal Year: 2020, Volume and Issue: 288(1), P. 56 - 80

Published: Sept. 22, 2020

Cellular senescence is a physiological mechanism whereby proliferating cell undergoes stable cycle arrest upon damage or stress and elicits secretory phenotype. This highly dynamic regulated cellular state plays beneficial roles in physiology, such as during embryonic development wound healing, but it can also result antagonistic effects age-related pathologies, degenerative disorders, ageing cancer. In an effort to better identify this complex state, given that universal marker has yet be identified, general set of hallmarks describing been established. However, the senescent programme becomes more defined, further complexities, including phenotype heterogeneity, have emerged. significantly complicates recognition evaluation senescence, especially within tissues living organisms. To address these challenges, substantial efforts are currently being made towards discovery novel specific biomarkers, optimized combinatorial strategies emerging detection techniques. Here, we compile advances present multifactorial guide assess cultures, The reliable assessment identification not only crucial for understanding its underlying biology, imperative diagnostic therapeutic aimed at targeting clinic.

Language: Английский

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Aging and age‐related diseases: from mechanisms to therapeutic strategies

Biogerontology, Journal Year: 2021, Volume and Issue: 22(2), P. 165 - 187

Published: Jan. 27, 2021

Language: Английский

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