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Kohlmeyer JL, Gordon DJ, Tanas MR, et al. Combination therapies for MPNSTs targeting RABL6A-RB1 signaling. Oncotarget. 2021;12(1):10-14doi: 10.18632/oncotarget.27862.
Kohlmeyer, J. L., Gordon, D. J., Tanas, M. R., Dodd, R. D., Monga, V., Darbro, B. W., & Quelle, D. E. (2021). Combination therapies for MPNSTs targeting RABL6A-RB1 signaling. Oncotarget, 12(1), 10-14. https://doi.org/10.18632/oncotarget.27862
Kohlmeyer, Jordan L, et al. "Combination therapies for MPNSTs targeting RABL6A-RB1 signaling." Oncotarget vol. 12,1 (2021): 10-14. doi: https://doi.org/10.18632/oncotarget.27862
Kohlmeyer JL, Gordon DJ, Tanas MR, Dodd RD, Monga V, Darbro BW, Quelle DE. Combination therapies for MPNSTs targeting RABL6A-RB1 signaling. Oncotarget. 2021 Jan 05;12(1):10-14. doi: 10.18632/oncotarget.27862. eCollection 2021 Jan 05. PMID: 33456709; PMCID: PMC7800773.
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Oncotarget. 2021 Jan 05;12(1):10-14. doi: 10.18632/oncotarget.27862. eCollection 2021 Jan 05.

Combination therapies for MPNSTs targeting RABL6A-RB1 signaling.

Oncotarget

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

Affiliations

  1. Molecular Medicine Graduate Program, University of Iowa, Iowa City, Iowa, USA.
  2. Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, USA.
  3. Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
  4. Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USA.
  5. Department of Pathology, University of Iowa, Iowa City, Iowa, USA.
  6. Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.

PMID: 33456709 PMCID: PMC7800773 DOI: 10.18632/oncotarget.27862

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.

Copyright: © 2021 Kohlmeyer et al.

Keywords: CDK4/6 and MEK inhibitors; MPNST; RABL6A-RB1 signaling; Ras; targeted cancer therapy

Conflict of interest statement

CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.

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