Discovery and Validation of Novel LonP1 and Proteasome Inhibitor in IDH1-R132H Malignant Astrocytoma Models

Douglas, Chris; Lomeli, Naomi; Lepe, Javier; Di, Kaijun; Nandwana, Nitesh Kumar; Vu, Thao; Pham, James; Kenney, M. Cristina; Das, Bhaskar C.; Bota, Daniela A.

doi:10.2139/ssrn.4354055

Cited by 1 publication

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“…D’Amico et al [ 67 ] revealed the modulation of the HIF signaling pathway by ADNP, reducing VEGF secretion and migration. Other factors such as M2 receptors, CXCR4, POL5551, LonP1, CT-L, PPARα, and SUMO are involved in regulating various aspects of glioblastoma progression and response to therapy, as noted by Cristofaro et al [ 69 ], Gagner et al [ 89 ], Douglas et al [ 72 ], Hofstetter et al [ 76 ], and Bernstock et al [ 83 ]. In addition, Lin et al [ 71 ] highlighted the far-reaching influence of HIF1α on tumor cell behavior, while Lin et al [ 88 ] investigated the regulation of pH-regulatory proteins in glioblastoma by hypoxia-induced HIF1α.…”

Section: Resultsmentioning

confidence: 99%

“…In their effort to target glioma cell proliferation and improve the efficacy of TMZ, Douglas et al [ 72 ] directed their research towards identifying a compound with the dual inhibition of LonP1 and CT-L. BT317 emerged as a promising candidate due to its ability to penetrate the blood–brain barrier, its low toxicity in animals, and its improved survival rates. However, in vivo tests with ritonavir led to the rapid development of resistance.…”

Section: Discussionmentioning

confidence: 99%

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Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review

Begagić,

Bečulić,

Džidić-Krivić

et al. 2024

Cancers

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Background: The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas. Methodology: The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction. Results: Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion. Conclusion: Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.

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