The Role and Therapeutic Targeting of JAK/STAT Signaling in Glioblastoma

SIMPLE SUMMARY: Glioblastoma is one of the most treatment-refractory human malignancies, and despite techniques that have allowed scientists and clinicians to better understand the molecular underpinnings of resistance, little progress has been made in improving the survival of patients with glioblastoma. We posit that dysregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling represents one major hub of tumorigenesis and resistance to medical therapies and that clinical study of its targeted inhibition is warranted, as well as highlighting the lessons learned from historical investigation going forward. ABSTRACT: Glioblastoma remains one of the deadliest and treatment-refractory human malignancies in large part due to its diffusely infiltrative nature, molecular heterogeneity, and capacity for immune escape. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes substantively to a wide variety of protumorigenic functions, including proliferation, anti-apoptosis, angiogenesis, stem cell maintenance, and immune suppression. We review the current state of knowledge regarding the biological role of JAK/STAT signaling in glioblastoma, therapeutic strategies, and future directions for the field.