ABSTRACT
Bladder cancer, which affects the bladder mucosa, is the ninth most common disease worldwide. There are manytypes of cancerous tissue in the bladder. Most exhibit low malignancy, but their recurrence rate is higher incomparison to more malignant tissues. Only 10%–15% progress to invasive bladder cancer and metastasize tothe lung, liver, and bone, which is significantly difficult to treat. The anticancer efficacy developed for the treatmentof highly malignant bladder cancer does not equally apply to all patients, and the side effects vary. To solvethis problem, studies have been conducted on various verification systems and patient-specific drug development.For example, an organ-on-a-chip model using patient cancer cells is being actively researched as an anticancerdrug verification system. A study on screening anticancer drugs according to cancer biomarkers unique to individualpatients is also in progress. In addition, studies have recently been conducted on immune anticancer drugs thatexhibit excellent anticancer efficacy. This report discusses various validation systems and drug screening criteriafor the development of patient-specific drugs. We propose that it is possible to evaluate the efficacy of anticancerdrugs for each patient, understand drug mechanism patterns in humans, and develop treatment that preventscancer metastasis.
ABSTRACT
BACKGROUND: Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. METHODS: Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting. RESULTS: Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest. CONCLUSIONS: Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.