The Hallmarks of Precancer

Overview

Journal Cancer Discov

Specialty Oncology

Date 2024 Apr 4

PMID 38571435

Authors

Mary M Stangis

Zhengyi Chen

Jimin Min

Sarah E Glass

Jordan O Jackson

Megan D Radyk

Xen Ping Hoi

W Nathaniel Brennen

Ming Yu

Huy Q Dinh

Robert J Coffey

Martha J Shrubsole

Keith S Chan

William M Grady

Srinivasan Yegnasubramanian

Costas A Lyssiotis

Anirban Maitra

Richard B Halberg

Neelendu Dey

Ken S Lau

Affiliations

Soon will be listed here.

Abstract

Research on precancers, as defined as at-risk tissues and early lesions, is of high significance given the effectiveness of early intervention. We discuss the need for risk stratification to prevent overtreatment, an emphasis on the role of genetic and epigenetic aging when considering risk, and the importance of integrating macroenvironmental risk factors with molecules and cells in lesions and at-risk normal tissues for developing effective intervention and health policy strategies.

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References

Min J, Zhang C, Bliton R, Caldwell B, Caplan L, Presentation K . Dysplastic Stem Cell Plasticity Functions as a Driving Force for Neoplastic Transformation of Precancerous Gastric Mucosa. Gastroenterology. 2022; 163(4):875-890. PMC: 9509466. DOI: 10.1053/j.gastro.2022.06.021. View

Chen Z, Lau K . Advances in Mapping Tumor Progression from Precancer Atlases. Cancer Prev Res (Phila). 2023; 16(8):439-447. PMC: 10523872. DOI: 10.1158/1940-6207.CAPR-22-0473. View

Taylor S, Falcone J, Cantley L, Goncalves M . Developing dietary interventions as therapy for cancer. Nat Rev Cancer. 2022; 22(8):452-466. DOI: 10.1038/s41568-022-00485-y. View

Carpenter E, Elhossiny A, Kadiyala P, Li J, McGue J, Griffith B . Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions. Cancer Discov. 2023; 13(6):1324-1345. PMC: 10236159. DOI: 10.1158/2159-8290.CD-23-0013. View

Saul D, Kosinsky R, Atkinson E, Doolittle M, Zhang X, LeBrasseur N . A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues. Nat Commun. 2022; 13(1):4827. PMC: 9381717. DOI: 10.1038/s41467-022-32552-1. View

Drapela S, Ilter D, Gomes A . Metabolic reprogramming: a bridge between aging and tumorigenesis. Mol Oncol. 2022; 16(18):3295-3318. PMC: 9490145. DOI: 10.1002/1878-0261.13261. View

Bell C, Lowe R, Adams P, Baccarelli A, Beck S, Bell J . DNA methylation aging clocks: challenges and recommendations. Genome Biol. 2019; 20(1):249. PMC: 6876109. DOI: 10.1186/s13059-019-1824-y. View

Zhou Y, Bian S, Zhou X, Cui Y, Wang W, Wen L . Single-Cell Multiomics Sequencing Reveals Prevalent Genomic Alterations in Tumor Stromal Cells of Human Colorectal Cancer. Cancer Cell. 2020; 38(6):818-828.e5. DOI: 10.1016/j.ccell.2020.09.015. View

Goncalves M, Lu C, Tutnauer J, Hartman T, Hwang S, Murphy C . High-fructose corn syrup enhances intestinal tumor growth in mice. Science. 2019; 363(6433):1345-1349. PMC: 6487857. DOI: 10.1126/science.aat8515. View

10.

Ma Z, Lytle N, Chen B, Jyotsana N, Novak S, Cho C . Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury. Gastroenterology. 2021; 162(2):604-620.e20. PMC: 8792222. DOI: 10.1053/j.gastro.2021.10.027. View

11.

Adkins-Threats M, Mills J . Cell plasticity in regeneration in the stomach and beyond. Curr Opin Genet Dev. 2022; 75:101948. PMC: 10378711. DOI: 10.1016/j.gde.2022.101948. View

12.

Noureldein M, Nawfal R, Bitar S, Maxwell S, Khurana I, Kassouf H . Intestinal microbiota regulates diabetes and cancer progression by IL-1β and NOX4 dependent signaling cascades. Cell Mol Life Sci. 2022; 79(9):502. PMC: 11802975. DOI: 10.1007/s00018-022-04485-x. View

13.

Chen X, Yi C, Yang M, Sun X, Liu X, Ma H . Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions. J Cancer. 2021; 12(5):1563-1574. PMC: 7847643. DOI: 10.7150/jca.54252. View

14.

Tomasetti C, Vogelstein B . Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015; 347(6217):78-81. PMC: 4446723. DOI: 10.1126/science.1260825. View

15.

Bu W, Liu Z, Jiang W, Nagi C, Huang S, Edwards D . Mammary Precancerous Stem and Non-Stem Cells Evolve into Cancers of Distinct Subtypes. Cancer Res. 2018; 79(1):61-71. PMC: 6318055. DOI: 10.1158/0008-5472.CAN-18-1087. View

16.

Singh V, Yeoh B, Chassaing B, Xiao X, Saha P, Aguilera Olvera R . Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell. 2018; 175(3):679-694.e22. PMC: 6232850. DOI: 10.1016/j.cell.2018.09.004. View

17.

Heaphy C, Gaonkar G, Peskoe S, Joshu C, De Marzo A, Lucia M . Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial. Prostate. 2015; 75(11):1160-6. PMC: 4475463. DOI: 10.1002/pros.22997. View

18.

Agathocleous M, Meacham C, Burgess R, Piskounova E, Zhao Z, Crane G . Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature. 2017; 549(7673):476-481. PMC: 5910063. DOI: 10.1038/nature23876. View

19.

Faget D, Ren Q, Stewart S . Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer. 2019; 19(8):439-453. DOI: 10.1038/s41568-019-0156-2. View

20.

Martincorena I, Fowler J, Wabik A, Lawson A, Abascal F, Hall M . Somatic mutant clones colonize the human esophagus with age. Science. 2018; 362(6417):911-917. PMC: 6298579. DOI: 10.1126/science.aau3879. View