Year: 2023
Type: editorial
Abstract: Editorial on the Research Topic Investigating drugs used off-label in various cancersCancer drug discovery is a long, expensive, drawn-out process involving the identification and optimization of lead compounds, followed by pre-clinical testing and clinical trials (1).It has been proved that its span varies between 11.4 to 13.5 years, and the costs range from 161 to 1800 million dollars from initial experiments to completed regulatory reviews (2, 3).Currently, more than 10,000 clinical trials investigating drug candidates in cancer are registered at www. clinicaltrials.gov.However, only a limited number of drug candidates progress to the next phase in clinical trials, with reports showing that less than 5% of drug compounds can be approved to enter phase I trials (4).Collectively, there is an urgent need to expand more discovery methods to remedy the growing anti-tumor medication needs gap.Drug repurposing or repositioning is the application of a drug for another indication than its original application (5).Discovering that already licensed medication readily available in the market affects diseases otherwise not knowingly attributed to these drug molecules avoids this research process.It can bring new, potentially life-saving treatments to patients with a cheaper cost and a faster path.However, repositioning the drug for further indication may accompany side effects not previously reported and will require validation in a new clinical trial.Nevertheless, the safety profile can be referred to as the initial indication, thus, increasing the likelihood of the drug through the trial (1).Recent clinic reports show that several epidemiological studies reveal lower cancer incidence in individuals receiving long-term psychotropic drug treatment.Varalda et al. investigated psychotropic drugs for their anti-tumor activity and evaluated their cytotoxic activity in colorectal carcinoma, glioblastoma, and breast cancer cell lines. The investigation revealed that penfluridol, ebastine, pimozide, fluoxetine, fluspirilene, and nefazodone have apparent cytotoxicity in all cancer cell lines tested in the low micromoles range. These psychotropic drugs caused mitochondrial membrane depolarization, increased the acidic vesicular compartments, and induced phospholipidosis in breast cancer MCF-7 cells. Varalda et al. showed that psychotropic drugs via dual targeting of lysosomes and mitochondria are a novel promising approach to cancer therapy, especially for cancer cells deficient in apoptotic machinery.Chlorpromazine has been used to treat psychiatric disorders for more than six decades.Clinic reports show that chlorpromazine is a potential anti-tumor medicine, but the mechanism is unclear.Matteoni et al. tested the anti-tumor effect of chlorpromazine in six glioblastoma cell lines.The results showed that chlorpromazine inhibited cancer cell viability in an apoptosisindependent way, induced hyperdiploidy, reduced cloning efficiency, neurosphere formation, and downregulated the expression of stemness genes.Furthermore, combining chlorpromazine with Frontiers in Oncology frontiersin.
Source: Frontiers in Oncology
Institution: University of Kansas Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4317106841