CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas

Janet R. Julson; Sara C. Horton; Colin H. Quinn; Andee M. Beierle; Laura V. Bownes; Jerry E. Stewart; Jamie Aye; Karina J. Yoon; Elizabeth A. Beierle

doi:10.1016/j.jpedsurg.2023.10.004

Back

CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas

Journal article

Peer reviewed

CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas

Janet R. Julson, Sara C. Horton, Colin H. Quinn, Andee M. Beierle, Laura V. Bownes, Jerry E. Stewart, Jamie Aye, Karina J. Yoon and Elizabeth A. Beierle

Journal of pediatric surgery, Vol.59(3), pp.473-482

03/2024

DOI: 10.1016/j.jpedsurg.2023.10.004

PMCID: PMC10922146

PMID: 37919169

Files and links (1)

url

https://pmc.ncbi.nlm.nih.gov/articles/PMC10922146/pdf/nihms-1936549.pdfView

Open Access

Abstract

Sarcomas are a heterogenous collection of bone and soft tissue tumors. The heterogeneity of these tumors makes it difficult to standardize treatment. CDK 4/6 inhibitors are a family of targeted agents which limit cell cycle progression and have been shown to be upregulated in sarcomas. In the current preclinical study, we evaluated the effects of lerociclib, a CDK4/6 inhibitor, on pediatric sarcomas in vitro and in 3D bioprinted tumors. The effects of lerociclib on viability, proliferation, cell cycle, motility, and stemness were assessed in established sarcoma cell lines, U-2 OS and MG-63, as well as sarcoma patient-derived xenografts (PDXs). 3D printed biotumors of each of the U-2 OS, MG-63, and COA79 cells were utilized to study the effects of lerociclib on tumor growth ex vivo. CDK 4/6, as well as the intermediaries retinoblastoma protein (Rb) and phosphorylated Rb were identified as targets in the four sarcoma cell lines. Lerociclib treatment induced cell cycle arrest, decreased proliferation, motility, and stemness of sarcoma cells. Treatment with lerociclib decreased sarcoma cell viability in both traditional 2D culture as well as 3D bioprinted microtumors. Inhibition of CDK 4/6 activity with lerociclib was efficacious in traditional 2D sarcoma cell culture as well as in 3D bioprints. Lerociclib holds promise and warrants further investigation as a novel therapeutic strategy for management of these heterogenous groups of tumors. •Sarcomas are a family of tumors which remain difficult to treat due to their heterogeneity and lack of adequate cell lines and models for study, especially in the pediatric population.•CDK 4/6 inhibition with agents such as lerociclib represent an example of targeted therapies amenable to high throughput testing via novel techniques such as 3D bioprinting.

3D bioprinting

CDK 4/6 inhibitors

Lerociclib

Pediatric sarcomas

Details

Title: Subtitle: CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas
Creators: Janet R. Julson - University of Alabama at Birmingham
Sara C. Horton - University of Alabama at Birmingham
Colin H. Quinn - University of Alabama at Birmingham
Andee M. Beierle - University of Alabama at Birmingham
Laura V. Bownes - University of Alabama at Birmingham
Jerry E. Stewart - University of Alabama at Birmingham
Jamie Aye - University of Alabama at Birmingham
Karina J. Yoon - University of Alabama at Birmingham
Elizabeth A. Beierle - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: Journal of pediatric surgery, Vol.59(3), pp.473-482
DOI: 10.1016/j.jpedsurg.2023.10.004
PMID: 37919169
PMCID: PMC10922146
NLM abbreviation: J Pediatr Surg
ISSN: 0022-3468
eISSN: 1531-5037
Publisher: Elsevier Inc
Number of pages: 10
Language: English
Date published: 03/2024
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984701650502771

Metrics

12 Record Views

1 Times Cited - Web of Science