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CDK8 remodels the tumor microenvironment and promotes resistance to KRASG12D inhibitors and daraxonrasib in PDAC.

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Title: CDK8 remodels the tumor microenvironment and promotes resistance to KRASG12D inhibitors and daraxonrasib in PDAC.
Authors: McAndrews KM; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Mahadevan KK; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Li B; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Comptdaer AM; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sockwell AM; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Morse SJ; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kelly PJ; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Patel SI; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kirtley ML; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Moreno Diaz BA; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lyu H; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Peng DH; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Khazaei S; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Schalck A; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhou X; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sugimoto H; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bickert AA; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sthanam LK; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Taylor MR; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kumbhar SV; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Arian KA; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Barekatain Y; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Paradiso F; Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Guerrero PA; Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bernard V; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sobhani N; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Camacho-Acevedo AN; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bornes KE; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Tran PT; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Maitra A; Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Heffernan TP; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kalluri R; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA. rkalluri@mdanderson.org.; Department of Bioengineering, Rice University, Houston, TX, USA. rkalluri@mdanderson.org.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. rkalluri@mdanderson.org.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. rkalluri@mdanderson.org.
Source: The EMBO journal [EMBO J] 2026 Jul 11. Date of Electronic Publication: 2026 Jul 11.
Publication Type: Journal Article
Journal Info: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
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  Data: CDK8 remodels the tumor microenvironment and promotes resistance to KRAS<superscript>G12D</superscript> inhibitors and daraxonrasib in PDAC.
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TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Peng+DH%22">Peng DH</searchLink>; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Khazaei+S%22">Khazaei S</searchLink>; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Schalck+A%22">Schalck A</searchLink>; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Zhou+X%22">Zhou X</searchLink>; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Sugimoto+H%22">Sugimoto H</searchLink>; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Bickert+AA%22">Bickert AA</searchLink>; 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Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Paradiso+F%22">Paradiso F</searchLink>; Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Guerrero+PA%22">Guerrero PA</searchLink>; Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Bernard+V%22">Bernard V</searchLink>; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Sobhani+N%22">Sobhani N</searchLink>; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Camacho-Acevedo+AN%22">Camacho-Acevedo AN</searchLink>; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Bornes+KE%22">Bornes KE</searchLink>; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Tran+PT%22">Tran PT</searchLink>; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Maitra+A%22">Maitra A</searchLink>; Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Heffernan+TP%22">Heffernan TP</searchLink>; TRACTION Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.<br /><searchLink fieldCode="AU" term="%22Kalluri+R%22">Kalluri R</searchLink>; Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA. rkalluri@mdanderson.org.; Department of Bioengineering, Rice University, Houston, TX, USA. rkalluri@mdanderson.org.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. rkalluri@mdanderson.org.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. rkalluri@mdanderson.org.
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