Precision medicine and phosphoproteomics for the identification of novel targeted therapeutic avenues in sarcomas

Ashleigh M Fordham; Paul G Ekert; Emmy D G Fleuren

doi:10.1016/j.bbcan.2021.188613

Precision medicine and phosphoproteomics for the identification of novel targeted therapeutic avenues in sarcomas

Biochim Biophys Acta Rev Cancer. 2021 Dec;1876(2):188613. doi: 10.1016/j.bbcan.2021.188613. Epub 2021 Aug 11.

Authors

Ashleigh M Fordham¹, Paul G Ekert², Emmy D G Fleuren³

Affiliations

¹ Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia.
² Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
³ Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia; University of New South Wales Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia. Electronic address: efleuren@ccia.org.au.

PMID: 34390800
DOI: 10.1016/j.bbcan.2021.188613

Abstract

Rapid advances in genomic technologies have enabled in-depth interrogation of cancer genomes, revealing novel and unexpected therapeutic targets in many cancer types. Identifying actionable dependencies in the diverse and heterogeneous group of sarcomas, particularly those that occur in children or adolescents and young adults (AYAs), remains especially challenging. These patients rarely harbor actionable genomic aberrations, no targeted agent is approved, and outcomes have remained poor for the past decades. This underlines a clear need to refine our methods for target identification. Phosphoproteomics studies in sarcoma showed the power of such analyses to capture novel actionable drivers that are not accompanied by mutational events or gene amplifications. This Review makes the case that incorporating phosphoproteomic molecular profiling alongside (functional) genomics technologies can significantly expand therapeutic target identification, and pinpoint drug mechanisms of action, in pediatric and AYA sarcoma patients. We explore the utility and prospects of phosphoproteomics in personalized medicine.

Keywords: Kinases; Pediatric sarcoma; Phosphoproteomics; Precision medicine; Sarcoma; Targeted therapies.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Female
Humans
Male
Precision Medicine / methods*
Proteomics / methods*
Sarcoma / pathology
Sarcoma / therapy*