Toward a systems-level probing of tumor clonality

Emanuelle I. Grody, Ajay Abraham, Vipul Shukla*, Yogesh Goyal*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Cancer has been described as a genetic disease that clonally evolves in the face of selective pressures imposed by cell-intrinsic and extrinsic factors. Although classical models based on genetic data predominantly propose Darwinian mechanisms of cancer evolution, recent single-cell profiling of cancers has described unprecedented heterogeneity in tumors providing support for alternative models of branched and neutral evolution through both genetic and non-genetic mechanisms. Emerging evidence points to a complex interplay between genetic, non-genetic, and extrinsic environmental factors in shaping the evolution of tumors. In this perspective, we briefly discuss the role of cell-intrinsic and extrinsic factors that shape clonal behaviors during tumor progression, metastasis, and drug resistance. Taking examples of pre-malignant states associated with hematological malignancies and esophageal cancer, we discuss recent paradigms of tumor evolution and prospective approaches to further enhance our understanding of this spatiotemporally regulated process.

Original languageEnglish (US)
Article number106574
Issue number5
StatePublished - May 19 2023


  • Cancer
  • Cancer systems biology
  • Immunology

ASJC Scopus subject areas

  • General


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