Treating Brain Cancer with a $50 Antidepressant? Drug Repurposing in Glioblastoma

Imagine finding the Holy Grail on a dusty shelf. This video delves into drug repurposing, a promising approach that saves time and cost by using approved medications for new diseases. We explore temozolomide, our main weapon against the aggressive brain cancer glioblastoma - its synthesis, mechanism and why it just barely extends survival. New research shows antidepressants like vortioxetine might have value as add-on therapies. Could this unexpected duo be the next step or even cure in the fight against glioblastoma?

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00:00 A cure to glioblastoma? Video overview
00:42 Drug repurposing or repositioning
02:27 The blood brain barrier
03:19 Glioblastoma, the worst (brain) cancer?
04:30 Chemotherapy for glioblastoma
05:08 Temozolomide is explosive
06:12 The big problem
06:46 Pls sub, thx
07:03 Mechanism of action of temozolomide
10:25 MGMT, the key enzyme
13:25 Pharmaceuticals as diazomethane surrogates?
14:11 Can antidepressants cure brain cancer? Methodology
16:55 Vortioxetine and its promising effects
19:13 No self-medication
19:42 Mibefradil, an interesting wild card
20:09 CAR-T in glioblastoma (chimeric antigen receptor T-cells)
21:19 Thanks for watching!

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Key references:
-- High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity | Nat Med (2024). https://doi.org/10.1038/s41591-024-03...
Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond | Nat Rev Drug Discov. 2006, 5, 689
Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives | Cancers 2022, 14, 443
Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial | Lancet Oncology 2009, 10, 459
Importance of Thermal Stability Data to Avoid Dangerous Reagents: Temozolomide Case Study | Org. Process Res. Dev. 2021, 25, 1690
O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas | Cell Death and Disease 2013, 4, e876
Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma | J Clin Oncol 2010, 28, 4601
Novel Imidazotetrazine Evades Known Resistance Mechanisms and Is Effective against Temozolomide-Resistant Brain Cancer in Cell Culture | ACS Chemical Biology 2022, 17, 299
Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations | Angew Chem Int Ed Engl 2020, 59, 1857
Antidepressants and survival in glioma—A registry-based retrospective cohort study | Neuro-Oncology Practice 2024, 11, 125
Targeting glioblastoma signaling and metabolism with a re-purposed brain-penetrant drug | Cell Reports 2021, 37, 109957