Targeting metabolic dependencies in pediatric cancer

Abstract

Purpose of Review: In an attempt to identify potential new therapeutic targets, efforts to describe the metabolic features unique to cancer cells are increasingly being reported. While current standard of care regimens for several pediatric malignancies incorporate agents that target tumor metabolism, these drugs have been part of the therapeutic landscape for decades. More recent research has focused on the identification and targeting of new metabolic vulnerabilities in pediatric cancers. The purpose of this review is to describe the most recent translational findings in the metabolic targeting of pediatric malignancies. Recent Findings: Across multiple pediatric cancer types, dependencies on a number of key metabolic pathways have emerged through study of patient tissue samples and preclinical modeling. Among the potentially targetable vulnerabilities are glucose metabolism via glycolysis, oxidative phosphorylation, amino acid and polyamine metabolism, and NAD + metabolism. While few agents have yet to move forward into clinical trials for pediatric cancer patients, the robust and promising preclinical data that has been generated suggests that future clinical trials should rationally test metabolically-targeted agents for relevant disease populations. Summary: Recent advances in our understanding of the metabolic dependencies of pediatric cancers represent a source of potential new therapeutic opportunities for these diseases.

Glucosylated Hybrid TiO2/Polymer Nanomaterials for Actively Targeted Sonodynamic Therapy of Cancer

“…This ligand has shown very high active targeting efficiency of PEO‐PPO polymeric micelles loaded with tyrosine kinase inhibitors in different patient‐derived pediatric sarcomas that overexpress glucose transporter‐1 (GLUT‐1) and resulted in improved therapeutic efficacy, while concomitantly reducing off‐target toxicity. [ 27 ] In this framework, we hypothesized that the intravenous (i.v.) administration of glucosylated aTiO 2 /PEO‐PPO (glu‐aTiO 2 /PEO‐PPO) nanomaterials of tuned sized followed by local US treatment will lead to a substantial improvement of the SDT of solid tumors overexpressing GLUTs (Figure 1d–f).…”

A prognostic NAD+ metabolism-related gene signature for predicting response to immune checkpoint inhibitor in glioma

“…By causing metabolic stress, inhibition of NAMPT offers a novel therapeutic approach in tumors that lack NAPRT expressions, such as glioblastoma and lymphoma. At the same time, normal cells are saved by NA by activating the NAPRT pathway (28)(29)(30). The fourth key gene, NMNAT3, is a member of the NMNAT family.…”

Transcriptome analysis reveals effects of leukemogenic SHP2 mutations in biosynthesis of amino acids signaling

“…Indeed, like glucose, there are major differences in the uptake and secretion of several amino acids in tumors relative to normal tissues. Compared to normal tissues, tumors require a large number of amino acids for bioenergetic, biosynthetic, and redox balance support ( 26 , 27 ). This high demand is not limited to essential amino acids, but also for nonessential amino acids (NEAA) ( 24 , 27 ).…”