Hallmarks of Cancer: New Dimensions

Cancer Discovery, Год журнала: 2022, Номер 12(1), С. 31 - 46

Опубликована: Янв. 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.

Язык: Английский

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Metastasis

Cell, Год журнала: 2023, Номер 186(8), С. 1564 - 1579

Опубликована: Апрель 1, 2023

Язык: Английский

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Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment

Nature Genetics, Год журнала: 2022, Номер 54(8), С. 1192 - 1201

Опубликована: Авг. 1, 2022

Язык: Английский

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Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Nature Cancer, Год журнала: 2022, Номер 3(4), С. 386 - 401

Опубликована: Апрель 28, 2022

Язык: Английский

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Metastasis-Initiating Cells and Ecosystems

Cancer Discovery, Год журнала: 2021, Номер 11(4), С. 971 - 994

Опубликована: Апрель 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.

Язык: Английский

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p53 and Tumor Suppression: It Takes a Network

Trends in Cell Biology, Год журнала: 2021, Номер 31(4), С. 298 - 310

Опубликована: Янв. 28, 2021

Язык: Английский

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A single-cell Arabidopsis root atlas reveals developmental trajectories in wild-type and cell identity mutants

Developmental Cell, Год журнала: 2022, Номер 57(4), С. 543 - 560.e9

Опубликована: Фев. 1, 2022

In all multicellular organisms, transcriptional networks orchestrate organ development. The Arabidopsis root, with its simple structure and indeterminate growth, is an ideal model for investigating the spatiotemporal signatures underlying developmental trajectories. To map gene expression dynamics across root cell types time, we built a comprehensive, organ-scale atlas at single-cell resolution. addition to estimating progressions in pseudotime, employed mathematical concept of optimal transport infer trajectories identify their regulators. demonstrate utility interpret new datasets, profiled mutants two key regulators resolution, shortroot scarecrow. We report transcriptomic vivo evidence tissue trans-differentiation mixed identity phenotype Our results support as rich community resource unraveling programs that specify maintain regulate

Язык: Английский

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Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Journal of Hepatology, Год журнала: 2021, Номер 75(6), С. 1397 - 1408

Опубликована: Июнь 30, 2021

Язык: Английский

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Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution

Cell, Год журнала: 2022, Номер 185(11), С. 1905 - 1923.e25

Опубликована: Май 1, 2022

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth expansion to neighboring distal tissues. The study phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout mouse model Kras;Trp53(KP)-driven lung adenocarcinoma tracked tumor from single-transformed metastatic tumors at unprecedented resolution. We found loss initial, stable alveolar-type2-like state was accompanied transient increase in plasticity. This followed adoption distinct transcriptional programs rapid and, ultimately, clonal sweep subclones capable metastasizing. Finally, develop through stereotypical evolutionary trajectories, perturbing additional suppressors accelerates progression creating novel trajectories. Our elucidates hierarchical nature more broadly, enables in-depth studies progression.

Язык: Английский

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Genetic and non-genetic clonal diversity in cancer evolution

Nature reviews. Cancer, Год журнала: 2021, Номер 21(6), С. 379 - 392

Опубликована: Март 16, 2021

Язык: Английский

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