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Annual Review of Cancer Biology

Volume 9, 2025

Lineage-Specific Transcription Factors in Carcinogenesis

  • Charles J. David1,2 and Sakari Vanharanta3,4
  • 1Tsinghua University School of Medicine, Beijing, China; email: [email protected] 2Peking University–Tsinghua Center for Life Sciences, Beijing, China 3Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; email: [email protected] 4Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  • Vol. 9:99-117 (Volume publication date April 2025)
  • First published as a Review in Advance on October 30, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Each cancer is the result of an individually unique evolutionary process. Yet, as demonstrated by extensive genetic analyses of human specimens, the genetic endpoints of cancers across different tissues are remarkably specific, with individual cancer driver genes being typically associated with only a limited set of tumor types. Tissue and cellular contexts thus impose strong and genetically predictable evolutionary constraints on carcinogenesis. Lineage-specific transcription factors, central regulators of organismal development, tissue homeostasis, and regeneration, often also support cancer cell fitness in a lineage-specific manner. In this review, we discuss recent results on the interactions between transcriptional lineage factor programs and oncogenic pathways and how such interactions may determine the oncogenic competence of cancer-associated genetic alterations. These developments are starting to shed light on the molecular basis of tissue specificity in carcinogenesis, with relevance for cancer prevention and therapy.

Keyword(s): cancer, cell lineage, cell state, oncogenic mutation, therapy resistance, tissue regeneration, transcription factor
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2025-04-11
2025-06-20
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Lineage-Specific Transcription Factors in Carcinogenesis
Annual Review of Cancer Biology 9, 99 (2025); https://doi.org/10.1146/annurev-cancerbio-060524-105603
/content/journals/10.1146/annurev-cancerbio-060524-105603
/content/journals/10.1146/annurev-cancerbio-060524-105603
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