Combination therapies for MPNSTs targeting RABL6A-RB1 signaling
| Autor: | Varun Monga, Munir R. Tanas, Rebecca D. Dodd, David Gordon, Jordan L. Kohlmeyer, Benjamin W. Darbro, Dawn E. Quelle |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Druggability GTPase targeted cancer therapy law.invention 03 medical and health sciences 0302 clinical medicine MPNST Cyclin-dependent kinase law medicine biology Kinase Retinoblastoma business.industry CDK4/6 and MEK inhibitors Cancer Precision medicine medicine.disease 030104 developmental biology RABL6A-RB1 signaling Oncology 030220 oncology & carcinogenesis Research Perspective Cancer research biology.protein Suppressor business Ras |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Precision medicine relies on a detailed molecular understanding of disease pathogenesis. Here, we consider urgently needed therapeutic options for malignant peripheral nerve sheath tumors (MPNSTs) based on emerging insights into druggable pathway alterations found to drive this deadly cancer. Recent observations demonstrate an essential role for an oncogenic GTPase, RABL6A, in promoting MPNST progression through hyperactivation of cyclin-dependent kinases (CDKs) and inactivation of the retinoblastoma (RB1) tumor suppressor. Monotherapies with CDK4/6 inhibitors have shown limited efficacy and durability in pre-clinical studies of MPNSTs and in clinical studies of other tumors. Therefore, we discuss the rationale and clinical benefits of inhibiting multiple RABL6A effectors, particularly CDK4/6 and MEK kinases, in targeted combination therapies suitable for MPNSTs and other Ras-driven malignancies. |
| Databáze: | OpenAIRE |
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