Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem DOI Creative Commons
Weiren Luo

Theranostics, Journal Year: 2023, Volume and Issue: 13(5), P. 1607 - 1631

Published: Jan. 1, 2023

Nasopharyngeal carcinoma (NPC) is a particular entity of head neck cancer that generally regarded as genetic disease with diverse intertumor and intratumor heterogeneity. This perspective review mainly outlines the up-to-date knowledge ecology NPC progression, presents number conceptual stepping-stones. At beginning, I explicitly advocate nature (cancer) not but an ecological disease: multidimensional spatiotemporal "unity evolution" pathological ecosystem. The hallmarks proposed to act factors population fitness. Subsequently, cells are described invasive species its metastasis multidirectional dispersal. foundational principles include intraspecific relationship (e.g. communication) interspecific competition, predation, parasitism mutualism) interpreted understand progression. "Mulberry-fish-ponds" model can well illustrate dynamic reciprocity Tumor-host interface transition zone cancer, tumor buddings should be recognized islands separated from mainland. It noted tumor-host has significantly molecular functional edge effect because curvature irregularity. Selection driving therapy including hyperthermia for patients, future perspectives in such field "ecological pathology", "multidimensional tumoriecology" also discussed. advance "nothing evolution or makes sense except light other". tree constructed comprehensively point out research direction. Taken together, establishment theory might provide novel framework paradigm our understanding complex causal process potential preventive therapeutic applications patients.

Language: Английский

Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology DOI Creative Commons

Luiz G. Almeida,

Hayley Thode,

Yekta Eslambolchi

et al.

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 74(3), P. 714 - 770

Published: June 23, 2022

The first matrix metalloproteinase (MMP) was discovered in 1962 from the tail of a tadpole by its ability to degrade collagen. As their name suggests, metalloproteinases are proteases capable remodeling extracellular matrix. More recently, MMPs have been demonstrated play numerous additional biologic roles cell signaling, immune regulation, and transcriptional control, all which unrelated degradation In this review, we will present milestones major discoveries MMP research, including various clinical trials for use inhibitors. We discuss reasons behind failures most inhibitors treatment cancer inflammatory diseases. There still misconceptions about pathophysiological best strategies inhibit detrimental functions. This review aims preclinical models human pathologies. new biochemical tools track proteolytic activity vivo ex vivo, addition future pharmacological alternatives functions

Significance Statement

Matrix (MMPs) implicated inflammatory, autoimmune, cancers, pathogen-mediated Initially overlooked, contributions can be both beneficial disease progression resolution. Thousands substrates suggested, few hundred validated. After more than 60 years there remain intriguing enigmas solve regarding biological

Language: Английский

Citations

279
Minimal functional driver gene heterogeneity among untreated metastases DOI Open Access
Johannes G. Reiter, Alvin Makohon‐Moore, Jeffrey M. Gerold

et al.

Science, Journal Year: 2018, Volume and Issue: 361(6406), P. 1033 - 1037

Published: Sept. 6, 2018

Metastases are responsible for the majority of cancer-related deaths. Although genomic heterogeneity within primary tumors is associated with relapse, among treatment-naïve metastases has not been comprehensively assessed. We analyzed sequencing data 76 untreated from 20 patients and inferred cancer phylogenies breast, colorectal, endometrial, gastric, lung, melanoma, pancreatic, prostate cancers. found that individual patients, a large driver gene mutations common to all metastases. Further analysis revealed were shared by unlikely have functional consequences. A mathematical model tumor evolution metastasis formation provides an explanation observed homogeneity. Thus, single biopsies capture most functionally important in therefore provide essential information therapeutic decision-making.

Language: Английский

Citations

272
Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma DOI
Lichun Ma, Limin Wang, Subreen A. Khatib

et al.

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 75(6), P. 1397 - 1408

Published: June 30, 2021

Language: Английский

Citations

236
Updating the Definition of Cancer DOI Creative Commons
Joel S. Brown, Sarah R. Amend, Robert H. Austin

et al.

Molecular Cancer Research, Journal Year: 2023, Volume and Issue: 21(11), P. 1142 - 1147

Published: July 6, 2023

Abstract Most definitions of cancer broadly conform to the current NCI definition: “Cancer is a disease in which some body's cells grow uncontrollably and spread other parts body.” These tend describe what “looks like” or “does” but do not “is” “has become.” While reflecting past insights, have kept pace with understanding that cell itself transformed evolving. We propose revised definition cancer: Cancer uncontrolled proliferation by subject evolution natural selection. believe this captures essence majority previous definitions. To simplest as cells, our adds adjective “transformed” capture many tumorigenic processes adopt metastasize. concept proposed then “subject selection.” The selection modernizes include genetic epigenetic changes accumulate within population lead lethal phenotype.

Language: Английский

Citations

236
Overview on Clinical Relevance of Intra-Tumor Heterogeneity DOI Creative Commons
Giorgio Stanta, Serena Bonin

Frontiers in Medicine, Journal Year: 2018, Volume and Issue: 5

Published: April 6, 2018

Today clinical evaluation of tumor heterogeneity today is an emergent issue to improve oncology. In particular, intra-tumor (ITH) closely related cancer progression, resistance therapy, and recurrences. It interconnected with complex molecular mechanisms including spatial temporal phenomena, which are often peculiar for every single patient. This review tries describe all the types ITH morpho-histological ITH, at level clonal derived from genomic instability non-clonal micro-environment interaction. important consider different as a whole any patient investigate on prognosis treatment opportunities. From practical point view analytical methods that widely accessible today, or will be in near future, evaluated pattern reproducible way application.

Language: Английский

Citations

222
Understanding tumor ecosystems by single-cell sequencing: promises and limitations DOI Creative Commons
Xianwen Ren, Boxi Kang, Zemin Zhang

et al.

Genome biology, Journal Year: 2018, Volume and Issue: 19(1)

Published: Dec. 1, 2018

Cellular heterogeneity within and across tumors has been a major obstacle in understanding treating cancer, the complex is masked if bulk tumor tissues are used for analysis. The advent of rapidly developing single-cell sequencing technologies, which include methods related to genome, epigenome, transcriptome, multi-omics sequencing, have applied cancer research led exciting new findings fields evolution, metastasis, resistance therapy, microenvironment. In this review, we discuss recent advances limitations these technologies their potential applications studies.

Language: Английский

Citations

197
Towards Multidrug Adaptive Therapy DOI Open Access
Jeffrey West, You Li, Jingsong Zhang

et al.

Cancer Research, Journal Year: 2020, Volume and Issue: 80(7), P. 1578 - 1589

Published: Jan. 16, 2020

A new ecologically inspired paradigm in cancer treatment known as "adaptive therapy" capitalizes on competitive interactions between drug-sensitive and drug-resistant subclones. The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing significant population treatment-sensitive cells survive. These, turn, suppress proliferation the less-fit resistant populations. However, there remain several open challenges designing therapies, particularly extending these therapeutic concepts multiple treatments. We present case study (metastatic castrate-resistant prostate cancer) point departure illustrate three novel aid design multidrug therapies. First, frequency-dependent "cycles" evolution can trap periodic, loop. Second, availability selection treatments may limit evolutionary "absorbing region" reachable tumor. Third, velocity significantly influences optimal timing drug sequences. These conceptual advances provide path forward for therapy. SIGNIFICANCE: Driving into repeatable cycles provides

Language: Английский

Citations

177
An analysis of genetic heterogeneity in untreated cancers DOI
Johannes G. Reiter, Marina Baretti, Jeffrey M. Gerold

et al.

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(11), P. 639 - 650

Published: Aug. 27, 2019

Language: Английский

Citations

173
Tumour heterogeneity and the evolutionary trade-offs of cancer DOI
Jean Hausser, Uri Alon

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(4), P. 247 - 257

Published: Feb. 24, 2020

Language: Английский

Citations

169
Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients DOI Creative Commons
Iva Truxová, Lenka Kašíková, Michal Hensler

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2018, Volume and Issue: 6(1)

Published: Dec. 1, 2018

A high density of tumor-infiltrating CD8+ T cells and CD20+ B correlates with prolonged survival in patients a wide variety human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact mature dendritic (DCs) shaping immune contexture HGSC, their role establishment cell-dependent antitumor immunity, prognostic value for HGSC remain unclear. We harnessed immunohistochemical tests biomolecular analyses to demonstrate that DC-LAMP+ DCs is robustly associated an characterized by TH1 polarization cytotoxic activity. showed both play critical generation clinically-favorable response microenvironment. In line this notion, robust tumor infiltration was most favorable overall two independent cohorts chemotherapy-naïve patients. Our findings suggest presence mature, microenvironment may represent novel, powerful biomarker reflects activation clinically-relevant anticancer immunity.

Language: Английский

Citations

165