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Updated: Jul 25, 2025

Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets
07:08

Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets

Published on: February 2, 2024

857

Chemical genomics reveals targetable programs of human cancers rooted in pluripotency

Luca Orlando1, Yannick D Benoit2, Jennifer C Reid1

  • 1Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

Cell Chemical Biology
|June 28, 2023
PubMed

Insights

Human pluripotent stem cells (hPSCs) share molecular profiles with adult tumors. Germ layer specification in hPSCs reveals cancer targets, with drugs selectively suppressing tumors based on their germ layer origin.

Area of Science:

  • Developmental Biology
  • Cancer Biology
  • Chemical Genomics

Background:

  • Overlapping principles exist between embryonic and tumor biology.
  • Multi-omics studies reveal shared molecular profiles between human pluripotent stem cells (hPSCs) and adult tumors.
  • Early germ layer fate decisions in hPSCs may offer insights into cancer biology.

Purpose of the Study:

  • To investigate the link between hPSC germ layer specification and cancer targets.
  • To identify drugs that selectively target tumors based on their germ layer origin.
  • To explore the potential of hPSC differentiation pathways in cancer therapy.

Main Methods:

  • Utilized a chemical genomic approach to study hPSCs.
  • Performed single-cell deconstruction of hPSC subsets with transcriptional similarities to adult tumors.
  • Conducted chemical screening using a germ layer specification assay for hPSCs.

Main Results:

  • Identified drugs that selectively suppressed patient-derived tumors based on their germ layer origin.
  • Demonstrated that hPSC germ layer specification reveals targets relevant to human cancers.
  • Showed that transcriptional responses in hPSCs to germ layer inducing drugs can inform cancer target identification.

Conclusions:

  • Properties of adult tumors converge with hPSC drug-induced differentiation in a germ layer-specific manner.
  • This convergence expands understanding of cancer stemness and pluripotency.
  • Germ layer specification in hPSCs offers a novel strategy for identifying cancer therapeutic targets.
Keywords:
cancerchemical genomicsdifferentiationgerm layer developmentmolecular dissectionpluripotent stem cells

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