Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most common and deadliest brain tumor with unrelenting and rapid disease progression. The standard of care for GBM is surgical excision followed by radiation with concurrent and adjuvant temozolomide-centered chemotherapy (TMZ). Treatment failure and resistance is the rule and despite advances in imaging technology, early detection of treatment failure or impending resistance remains a challenge. There is a dire, unmet, need in clinical practice for minimally-invasive diagnostic tools to enable timely understanding of disease progression and treatment response. Here, we aim to address this clinical need by leveraging a unique characteristic of GBM: the overexpression of the α2 variant of the IL-13 receptor in over 75% of GBM tumors. METHODS: In this study we examined patients with primary GBM from Penn State and Cleveland Clinic compared to healthy controls. RESULTS: IL13Rα2 was detectable in plasma of GBM patients using ELISA but detection could be optimized by PEG precipitation to enrich for extracellular vesicles (EVs). Patients with GBM had elevated levels of plasma IL13Rα2, which correlated to levels of this receptor in the tumor tissue. Elevated plasma levels of IL13Rα2 predicted longer overall survival (OS) (19.8 vs. 13.2 months). Similarly, detection of IL13Rα2 + cells in tumor tissue also predicted longer OS (22.1 vs. 12.2 months). CONCLUSION: These findings strongly suggest that expression of the IL13Rα2 receptor confer survival advantage in GBM patients, which can be determined through a minimally-invasive liquid biopsy. Detection of plasma IL13Rα2 can also be used to select GBM patients for targeted tumor therapy.

Genetic Biomarkers in Astrocytoma: Diagnostic, Prognostic, and Therapeutic Potential.

Astrocytoma are the most common adult brain tumor, with Glioblastoma being the deadliest neuro-related malignancy. Despite advances in oncology, the prognosis for Astrocytoma, especially Glioblastoma, remains poor, and tracking disease progression is challenging due to a lack of robust biomarkers. Genetic biomarkers, including microRNAs, cell-free DNA, circulating tumor DNA, circular RNA, and long non-coding RNA (lncRNA), can serve as potential diagnostic and therapeutic targets. In this review, we examine the existing literature, analyzing the various less established liquid and tumor genetic biomarkers and their potential to act as diagnostic, prognostic, and therapeutic targets. We highlight the clinical challenges and limitations in implementing liquid biopsy strategies in clinical practice. The article discusses the potential of liquid biopsies as valuable tools for personalized Astrocytoma management while emphasizing the need for standardized protocols and further advancements to establish their clinical utility and therapeutic application.