Rethinking the microenvironment's role in chemical-induced malignancy.
| Title: | Rethinking the microenvironment's role in chemical-induced malignancy. |
|---|---|
| Authors: | Bisson WH; Integrative Toxicology and Cancer Prevention, Research Triangle Park, NC 27560, United States.; Currie RA; Syngenta Jealott's Hill International Research Centre, Bracknell RG42 6EY, United Kingdom.; Lim EL; Department of Biochemistry and Molecular Biology & Edwin SH Leong Centre for Healthy Aging, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.; Mlynarczyk C; Yale Cancer Center and Department of Internal Medicine, Yale University, New Haven, CT 06520, United States.; Tokar EJ; Division of Translational Toxicology, National Institute of Environmental Sciences, Research Triangle Park, NC 27560, United States.; Colacci A; Agency for Prevention, Environment and Energy, Emilia-Romagna (Arpae), Bologna 40122, Italy.; Alma Mater Institute on Healthy Planet, University of Bologna, Bologna 40138, Italy.; Colacino JA; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States.; Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States. |
| Source: | Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2026 Feb 18; Vol. 209 (2). |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9805461 Publication Model: Print Cited Medium: Internet ISSN: 1096-0929 (Electronic) Linking ISSN: 10960929 NLM ISO Abbreviation: Toxicol Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: 1999- : Cary, NC : Oxford University Press; Original Publication: Orlando, FL : Academic Press, c1998- |
| MeSH Terms: | Tumor Microenvironment*/drug effects ; Neoplasms*/chemically induced ; Neoplasms*/pathology ; Carcinogens*/toxicity; Humans ; Animals |
| Abstract: | Why and how does cancer start? Building from a Symposium at the 2025 Society of Toxicology meeting, we convened a group of international experts to answer this seemingly simple question. As experimental evidence has evolved, perspectives on cancers' origins have shifted from the accumulation of DNA mutations in single cells to complex processes involving signals from an altered tissue microenvironment which promote tumorigenesis. Carcinogen exposures impact the biology of the microenvironment in complex and tissue-specific ways. These changes can include the infiltration of inflammatory cells that produce growth factors, neo-angiogenesis, morphological changes, and immune tolerance that avoids immune-mediated elimination. In this in-depth review, we discuss the evidence linking chemical-driven microenvironmental changes in the development of a range of solid and liquid tumors. We discuss specific phenotypic alterations, such as selection pressure driving clonal expansion and cellular plasticity and reacquisition of stem cell states, linked to carcinogen-induced changes in the microenvironment. We describe assays and biomarkers which can allow us to experimentally assess links between chemical exposures, the microenvironment, and cancer phenotypes. We end by discussing how understanding the role of the microenvironment and malignancy in toxicology is essential for accurate cancer hazard evaluation, development of next-generation risk assessment frameworks, identifying new strategies for cancer prevention, and improving patient care.; (Published by Oxford University Press on behalf of the Society of Toxicology 2025.) |
| Grant Information: | NIH; NTA-PMT ZIA: ES103378-02 United States ES NIEHS NIH HHS |
| Contributed Indexing: | Keywords: biomarkers; cancer prevention; cancer risk assessment; microenvironment; promotion |
| Substance Nomenclature: | 0 (Carcinogens) |
| Entry Date(s): | Date Created: 20251217 Date Completed: 20260219 Latest Revision: 20260219 |
| Update Code: | 20260219 |
| DOI: | 10.1093/toxsci/kfaf174 |
| PMID: | 41405843 |
| Database: | MEDLINE |
Journal Article; Review