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Strength through diversity: how cancers thrive when clones cooperate.
Marije C Kuiken1,2, Maartje Witsen1,2, Emile E Voest1,2
1Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Molecular Oncology
|November 9, 2025
Summary
Cancer subclones can cooperate, not just compete. This clonal cooperation, driven by various factors, presents new therapeutic vulnerabilities and resistance mechanisms in cancer treatment.
Area of Science:
- Oncology
- Cancer Biology
- Genetics
Background:
- Cancer is characterized by intratumor heterogeneity, with multiple distinct subclones within a single tumor.
- Traditionally, subclones are viewed as competitors, but evidence suggests cooperation can also occur.
Purpose of the Study:
- To review existing evidence for clonal cooperativity in cancer.
- To address key questions and outline future developments regarding clonal cooperation.
- To highlight the clinical implications of interdependent cancer populations.
Main Methods:
- Literature review of existing evidence for clonal cooperativity.
- Analysis of six overarching principles governing clonal cooperation.
- Discussion of technological developments for therapeutic strategies.
Main Results:
- Secreted factors, small subclones, and both genetic/nongenetic heterogeneity mediate cooperation.
- Nonmalignant cells and cooperation across cancer stages (premalignancy to metastasis) are observed.
- Clonal cooperation can promote therapy resistance by protecting sensitive populations.
Conclusions:
- Clonal cooperation is a significant mechanism in cancer development and progression.
- Interdependent cancer populations present therapeutic vulnerabilities.
- Novel strategies targeting clonal cooperativity could exploit these vulnerabilities for cancer treatment.
Keywords:
cancer progressionclonal cooperationintratumoral heterogeneitysecreted factorstherapy resistanceMore Related Videos
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