Exploiting Glutamine Addiction: Liposomal Glutamine Overload as an Approach to Induce Autophagic Cell Death in Glioblastoma and Pancreatic Cancer

Many cancer cells exhibit a heightened dependence on the amino acid glutamine, a phenomenon termed 'glutamine addiction'. Glutamine is an amino acid and a key component in cancer cells because it supports their proliferation and survival; current therapeutic strategies and research focuses on glutamine deprivation or metabolic inhibition. We propose a counterintuitive approach: delivering supraphysiological concentrations of glutamine directly to tumor cells using formulated liposomes to cause autophagy-mediated cell death. This unique concept exploits the metabolic vulnerability of tumor cells while limiting systemic effects on the rest of the body by using a tumor-targeted delivery system. We will focus on the two specific cancers throughout this paper: glioblastoma multiforme (GBM) and pancreatic ductal adenocarcinoma (PDAC).This concept paper outlines the rationale, mechanistic basis, and proposed experimental framework for investigating glutamine overload as a possible novel metabolic therapy.