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

doi:10.1038/s44318-026-00854-5

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Article

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

The EMBO journal - 1 Aug 2026

McAndrews Kathleen M, Mahadevan Krishnan K, Li Bingrui, Comptdaer Anaïs M, Sockwell Amari M, Morse Sami J, Kelly Patience J, Patel Sarah I, Kirtley Michelle L, Moreno Diaz Barbara A, Lyu Hengyu, Peng David H, Khazaei Sima, Schalck Aislyn, Zhou Xunian, Sugimoto Hikaru, Bickert Aaron A, Sthanam Lakshmi Kavitha, Taylor Meagan R, Kumbhar Shreyasee V, Arian Kent A, Barekatain Yasaman, Paradiso Francesca, Guerrero Paola A, Bernard Vincent, Sobhani Navid, Camacho-Acevedo Alondra N, Bornes Kiara E, Tran Phuong Thao, Maitra Anirban, Heffernan Timothy P, Kalluri Raghu

Abstract excerpt

Mutations in KRAS are a dominant driver of pancreatic ductal adenocarcinoma (PDAC), with about 50% of patients presenting with KRASG12D mutations. Small molecule inhibitors targeting KRASG12D suppress PDAC; however, the contribution of the tumor microenvironment (TME) to the sustained efficacy of KRASG12D inhibition and mechanisms of resistance to KRASG12D suppression remain to be elucidated. Here, integrated...

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