Hedgehog signaling regulates the development and treatment of glioblastoma (Review)

Abstract

Glioblastoma (GBM) is the most common and fatal malignant tumor type of the central nervous system. GBM affects public health and it is important to identify biomarkers to improve diagnosis, reduce drug resistance and improve prognosis (e.g., personalized targeted therapies). Hedgehog (HH) signaling has an important role in embryonic development, tissue regeneration and stem cell renewal. A large amount of evidence indicates that both normative and non-normative HH signals have an important role in GBM. The present study reviewed the role of the HH signaling pathway in the occurrence and progression of GBM. Furthermore, the effectiveness of drugs that target different components of the HH pathway was also examined. The HH pathway has an important role in reversing drug resistance after GBM conventional treatment. The present review highlighted the relevance of HH signaling in GBM and outlined that this pathway has a key role in the occurrence, development and treatment of GBM. Contents 1. Introduction 2. Overview of GBM 3. The HH signaling pathway 4. Molecular mechanisms of the HH signaling pathway in GBM 5. Targeting the HH signaling pathway in GBM 6. HH pathway and immunotherapy 7. Discussion 8. Conclusion

SALIQ in Rhabdomyosarcoma: A Repurposed Multidrug Regimen to Augment Standard Treatments by Adding Simvastatin, All Trans Retinoic Acid, Lithium, Itraconazole, and Quercetin

“…Hh signaling engagement participates in facilitating growth and treatment resistance across a wide variety of cancers [102][103][104][105][106][107]. This is also the case in rhabdomyosarcoma [88,[108][109][110][111][112][113].…”

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies

“… 236 The overall survival of patients with glioblastoma is decreased by upregulation of Shh based on data from the Cancer Genome Atlas glioblastoma. 237 …”

Suppression of sonic hedgehog pathway-based proliferation in glioblastoma cells by small-size silver nanoparticles in vitro

“…Subsequently, the signal is transduced intracellularly (with engagement of the SUFU protein), resulting in the activation of the zinc finger protein (Gli1), a well-described oncogene, which stimulates cells to proliferate (Zhu and Lo 2010 ). Interestingly, alterations in the HH pathway have been linked with development of high-grade GBs as well as increased cancer invasiveness (Takezaki et al 2011 ; Wang et al 2022 ). Many efforts have been made to use the HH pathway as a target in the anti-GB treatment, e.g., the inhibition of the activity of the SMO protein, which was shown by Bissey et al to have failed during clinical trials (Bissey et al 2020 ).…”