2. Academic Validation
  3. Pan-cancer analysis reveals Rho kinase addiction as a vulnerability of de-differentiated cancer cells

Pan-cancer analysis reveals Rho kinase addiction as a vulnerability of de-differentiated cancer cells

  • iScience. 2026 Jun 2;29(6):116031. doi: 10.1016/j.isci.2026.116031.
Jaume Barcelo 1 2,  Yumiko Teigen 1 2,  Joshua Alexander James Martin 1 2,  Samantha George 1 2,  Dipanwita Das 1,  Joanne Sewell 2,  Anna Perdrix-Rosell 3,  Findlay Bewicke-Copley 4 5,  Ritobrata Ghose 1,  William Yang 6,  Rachel Brough 6,  Andrew Clear 4,  Wencke Walter 7,  Torsten Haferlach 7,  Ilaria Malanchi 3,  John G Gribben 4,  Louie N van de Lagemaat 8,  Kamil R Kranc 9,  Christopher J Lord 6,  Ana Rio-Machin 5 10,  Oscar Maiques 1 2 11,  Jude Fitzgibbon 5,  Victoria Sanz-Moreno 1 2
Affiliations

Affiliations

  • 1 Cytoskeleton and Cancer Metastasis Laboratory, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, UK.
  • 2 Centre for Tumor Microenvironment, Barts Cancer Institute, Queen Mary University of London, London, UK.
  • 3 Tumor-Host Interaction Laboratory, The Francis Crick Institute, London, UK.
  • 4 Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
  • 5 Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.
  • 6 Precision Oncology Laboratory, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, UK.
  • 7 MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany.
  • 8 Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Aberdeen, UK.
  • 9 The Institute of Cancer Research, Sutton, London, UK.
  • 10 Experimental Haematology Lab, IIS- Fundación Jimenez Díaz, UAM, Madrid, Spain.
  • 11 Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
PMID: 42369662 DOI: 10.1016/j.isci.2026.116031
Abstract

Although Rho kinase (ROCK) has been studied in tumor progression, the reliance of some Cancer cells on ROCK-Myosin II for survival remains poorly understood. Using systematic analysis of ROCK Inhibitor sensitivity in hundreds of Cancer cell lines, we find that ROCK inhibition reduces survival of highly de-differentiated, invasive Cancer cells from solid tumors. Transcriptomic analysis reveals enrichment in epithelial-to-mesenchymal transition, migration, proliferation, and inflammation genes, with reduced expression of differentiation and cell-cell junction genes like E-cadherin (CDH1). Acute myeloid leukemia (AML) shows high ROCK Inhibitor response among hematological malignancies. Using in vitro and in vivo approaches, we validate biomarkers of ROCK Inhibitor sensitivity in breast Cancer, melanoma, and AML, demonstrating their unique addiction to Rho-ROCK-myosin II signaling for survival. Our work has important pre-clinical implications while cautions against wider use of ROCK inhibitors in patient-derived Organoid cultures, where they may deplete important Cancer cell populations.

Keywords

cancer; therapeutics; transcriptomics.

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