Predicting success after laparoscopic heller myotomy: lessons from 22 years in a resource-limited context.

Glioblastoma (GB) represents the most prevalent and aggressive primary malignant brain tumor in adults. The current standard therapeutic strategy for newly diagnosed GB includes surgical resection followed by radiotherapy in combination with chemotherapeutic agents such as temozolomide (TMZ) []. TMZ exerts its anti‐tumor effect by adding methyl groups to DNA, most importantly at the O position of guanine. This specific lesion mispairs during DNA replication, triggering DNA damage responses that ultimately lead to tumor cell death. However, glioblastoma cells can counteract this effect through the DNA repair enzyme O‐methylguanine‐DNA methyltransferase (MGMT), which directly removes the methyl group and restores the DNA, thereby reducing the drug's cytotoxicity []. Drug repurposing, the process of finding new therapeutic uses for existing drugs, has many advantages over developing new drugs. It allows drugs to reach the clinic more quickly, as their safety and pharmacokinetic data are already available, reducing the need for initial testing. It also reduces research and development costs and may uncover new molecular targets and biological insights that expand the therapeutic potential of existing drugs [, ]. This review describes the therapeutic mechanisms and targeted pathways of repurposed drugs used in combination with TMZ, their mode of action, and their potential clinical applications for GB. This narrative review discusses agents that are approved for other indications in one or more jurisdictions, together with selected investigational agents that have been proposed as TMZ modulators, including: antimicrobials (e.g., chloroquine), central nervous system drugs (e.g., valproic acid), cardiovascular drugs (e.g., aspirin, amlodipine), antidiabetic drugs (e.g., metformin), lipid‐lowering drugs (e.g., atorvastatin), antipsychotics (e.g., chlorpromazine), opioids (e.g., methadone, morphine), antibiotics (e.g., nitroxoline, azithromycin, ciprofloxacin), benzodiazepines (e.g., diazepam), and SSRIs (e.g., fluoxetine), supplements (e.g., melatonin), hormone therapy (e.g., tamoxifen), anti‐alcoholism agents (e.g., disulfiram), proteasome inhibitors (e.g., marizomib, bortezomib), mTOR inhibitors (e.g., everolimus), and photodynamic therapy agents (e.g., verteporfin). This narrative review was based on a literature search of PubMed and Web of Science. Search terms included glioblastoma, glioma, temozolomide, drug repurposing, and the names of individual candidate drugs. Original preclinical and clinical studies evaluating repurposed drugs alone or in combination with temozolomide were included. Review articles were used to identify relevant primary studies. Studies unrelated to glioblastoma or lacking relevant outcome data were excluded. Preclinical and clinical findings were evaluated separately. These drugs may modulate key pathways involved in glioblastoma growth, survival, DNA repair, autophagy, and TMZ resistance, including MGMT, PI3K/AKT/mTOR, AMPK, EGFR, STAT3, ERK1/2, NF‐κB, and YAP/Hippo signaling pathways (Figure ; Table ). Furthermore, this review demonstrates the clinical importance of repurposed drugs and offers the potential to provide more effective and accessible treatment options for this highly aggressive tumor type.