Combination therapies for MPNSTs targeting RABL6A-RB1 signaling

Jordan L Kohlmeyer; David J Gordon; Munir R Tanas; Rebecca D Dodd; Varun Monga; Benjamin W Darbro; Dawn E Quelle

doi:10.18632/ONCOTARGET.27862

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Combination therapies for MPNSTs targeting RABL6A-RB1 signaling

Journal article

Open access

Peer reviewed

Combination therapies for MPNSTs targeting RABL6A-RB1 signaling

Jordan L Kohlmeyer, David J Gordon, Munir R Tanas, Rebecca D Dodd, Varun Monga, Benjamin W Darbro and Dawn E Quelle

Oncotarget, Vol.12(1), pp.10-14

01/05/2021

DOI: 10.18632/ONCOTARGET.27862

PMCID: PMC7800773

PMID: 33456709

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https://doi.org/10.18632/ONCOTARGET.27862View

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Abstract

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.

targeted cancer therapy

Ras

MPNST

CDK4/6 and MEK inhibitors

RABL6A-RB1 signaling

Details

Title: Subtitle: Combination therapies for MPNSTs targeting RABL6A-RB1 signaling
Creators: Jordan L Kohlmeyer - University of Iowa
David J Gordon - University of Iowa
Munir R Tanas - University of Iowa
Rebecca D Dodd - University of Iowa
Varun Monga - University of Iowa
Benjamin W Darbro - University of Iowa
Dawn E Quelle - University of Iowa
Resource Type: Journal article
Publication Details: Oncotarget, Vol.12(1), pp.10-14
DOI: 10.18632/ONCOTARGET.27862
PMID: 33456709
PMCID: PMC7800773
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: Impact Journals LLC
Grant note: P30 CA086862 / NCI NIH HHS
Language: English
Date published: 01/05/2021
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Pathology; Medical Genetics and Genomics; Hematology/Oncology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984186628902771

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