Novel therapeutic compounds for prostate adenocarcinoma treatment

Abstract

Introduction: Prostate adenocarcinoma is the most frequently diagnosed malignancy, particularly for people >70 years old. The main challenge in the treatment of advanced neoplasm is bone metastasis and therapeutic resistance for known oncology drugs. Novel treatment methods to prolong the survival time and improve the life quality of these specific patients are required. The present study attempted to screen potential therapeutic compounds for the tumor through bioinformatics approaches, in order to provide conceptual treatment for this malignant disease. Methods: Differentially expressed genes were obtained from the Gene Expression Omnibus database and submitted into the Connectivity Map database for the detection of potentially associated compounds. Target genes were extracted from the search results. Functional annotation and pathway enrichment were performed for the confirmation. Survival analysis was used to measure potential therapeutic effects. Results: It was revealed that 3 compounds (vanoxerine, tolnaftate, and gabexate) may help to prolong the disease-free survival time from tumor metastasis of patients with the tumor. A total of 6 genes [also-keto reductase family 1 member C3 (AKR1C3), collagen type III α 1 chain (COL3A1), lipoprotein lipase (LPL), glucuronidase, β pseudogene 11 (GUSBP11), apolipoprotein E (APOE), and collagen type I α 1 chain (COL1A1)] were identified to be the potential therapeutic targets for the aforementioned compounds. Conclusion: In the present study, it was speculated that 3 compounds may function as the potential therapeutic drugs of bone metastatic prostate adenocarcinoma; however, further studies verifying vitro and in vivo are necessary.

A Unified Transcriptional, Pharmacogenomic, and Gene Dependency Approach to Decipher the Biology, Diagnostic Markers, and Therapeutic Targets Associated with Prostate Cancer Metastasis

“…There are already various FDA-approved AR antagonists, including spironolactone, flutamide, bicalutamide, enzalutamide, darolutamide, apalutamide, and nilutamide. Other targets that have been associated with prostate cancer metastasis (or progression) include BIRC5/survivin [83], EZH2 [84], TOP2A [85,86], HMMR [87], LPL [88], and SSTR1 [89]. According to DrugBank, the potential inhibitors against the proteins mentioned above are reserpine and berberine for BIRC5, tazemetostat for EZH2, hyaluronic acid for HMMR, dactinomycin for TOP2A, pasireotide and somatostatin for SSTR1, and tyloxapol for LPL.…”