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ea0089b8 | Basic Science | NANETS2022

CDK4/6-MEK Targeted Therapy Causes Regression and Reduced Metastatic Colonization of Pancreatic Neuroendocrine Tumors

Kaemmer Courtney , Umesalma Shaikamjad , Maharjan Chandra , Kohlmeyer Jordan , Wilkerson Emily , Sheehy Ryan , Leidinger Mariah , Meyerholz David , Bell Sarah , Zamba Gideon , Breheny Patrick , Lattime Edmund , Chandrasekharan Chandrikha , Bellizzi Andrew , Herring Laura , Graves Lee , Darbro Benjamin , Yuan Ziqiang , Libutti Steven , Quelle Dawn

Background: New therapeutics and combinations are needed to improve the survival of patients with advanced, metastatic pancreatic NETs (pNETs). RABL6A is a novel oncogenic driver of pNET pathogenesis that acts through multiple oncogenic pathways. Kinome and phosphoproteome analyses of proliferating (RABL6A-positive) pNET cells, vs arrested (RABL6A-knockdown) controls, demonstrated that druggable cyclin-dependent kinase 4 and 6 (CDK4/6) and MEK kinases are activated in growing ...

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ea0098b28 | Basic Science | NANETS2023

Therapies targeting CDK4/6 cause regression, immune cell activation, and sensitization to PD-L1 immunotherapy in pancreatic neuroendocrine tumors

Kaemmer Courtney , Umesalma Shaikamjad , Maharjan Chandra , Kohlmeyer Jordan , Lingo Joshua , Wilkerson Emily , Sheehy Ryan , Leidinger Mariah , Meyerholz David , Bell Sarah , Zamba Gideon , Breheny Patrick , Lattime Edmund , Chandrasekharan Chandrikha , Bellizzi Andrew , Herring Laura , Graves Lee , Darbro Benjamin , Yuan Ziqiang , Libutti Steven , Quelle Dawn

Background: New effective therapies are needed to improve the survival of patients with metastatic pancreatic NETs (pNETs). RABL6A is a novel oncogenic driver of pNET pathogenesis. Kinome and phosphoproteome analyses of proliferating (RABL6A-positive) pNET cells, vs arrested (RABL6A-knockdown) controls, demonstrated that cyclin-dependent kinase 4 and 6 (CDK4/6) and MEK kinases are actionable drug targets in growing pNET cells. In agreement, published studies of patient pNETs b...

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Endocrine Abstracts

CDK4/6-MEK Targeted Therapy Causes Regression and Reduced Metastatic Colonization of Pancreatic Neuroendocrine Tumors

Therapies targeting CDK4/6 cause regression, immune cell activation, and sensitization to PD-L1 immunotherapy in pancreatic neuroendocrine tumors

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