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Exploiting tumor lineage features for precision cancer therapy.

Lois M Kelly1, Nina Fenouille1, Kris C Wood2

  • 1INSERM UMR 944, IRSL, St Louis Hospital, University of Paris-Cité, Paris, France.

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|January 3, 2026
PubMed
Summary

Cancer cells maintain their tissue of origin identity, influencing tumor behavior and vulnerabilities. Understanding these lineage-specific traits reveals new therapeutic targets and informs precision immunotherapies.

Keywords:
cancer specialized functionhigh-resolution mappinglineage dependencieslineage-tracing systemsprecision oncologytargeted therapiestissue-selective oncogenic driverstumor antigen repertoire for advanced T cell therapiestumor tissue of origin

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Area of Science:

  • Oncology
  • Developmental Biology
  • Genetics

Background:

  • Cancer cells often retain characteristics of their tissue of origin, established before malignant transformation.
  • Advances in single-cell and lineage-tracing technologies offer high-resolution insights into these cellular features.

Purpose of the Study:

  • To review recent technological advancements in mapping cancer cell lineage and tissue of origin.
  • To examine how the tissue of origin influences tumor behavior, genetic alterations, and therapeutic vulnerabilities.
  • To highlight the role of lineage-specific dependencies in identifying novel therapeutic targets and informing precision immunotherapies.

Main Methods:

  • Overview of single-cell and lineage-tracing technologies.
  • Analysis of how tissue of origin shapes oncogenic driver selection and genetic alterations.
  • Exploration of lineage-specific physiological functions and signaling pathways in cancer cells.
  • Examination of cell surface marker expression for precision immunotherapy.

Main Results:

  • The tissue of origin significantly shapes tumor genetic alterations and vulnerabilities.
  • Cancer cells remain dependent on lineage-specific functions and pathways.
  • Lineage-specific cell surface markers are crucial for developing precision immunotherapies.

Conclusions:

  • Understanding the developmental and functional identity of cancer cells is crucial for personalized therapy.
  • Lineage-specific insights are driving a paradigm shift towards tailored cancer treatments.
  • Targeting lineage-dependent vulnerabilities offers promising therapeutic strategies.