Combating anoikis resistance: bioactive compounds transforming prostate cancer therapy

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Prostate cancer (PCa) presents significant treatment challenges due to its complexity and acquired drug resistance.
• Identifying molecular targets like differentially expressed genes (DEGs) is crucial for developing effective therapies.

Purpose of the Study:

• To identify DEGs associated with PCa, including those related to anoikis resistance and circulating tumor cells.
• To screen bioactive compounds for a combination that can modulate the expression of identified DEGs.
• To investigate the therapeutic potential of this compound combination in controlling PCa progression.

Main Methods:

• Differential gene expression analysis was performed on PCa samples to identify 53 DEGs.
• Gene enrichment analysis was used to understand the functional roles of these DEGs.
• A library of 102 bioactive compounds was screened to find a synergistic combination targeting the DEGs.

Main Results:

• Fifty-three DEGs were identified, linked to anoikis resistance and circulating tumor cells in PCa.
• A combination of gastrodin, nitidine chloride, chenodeoxycholic acid, and bilobalide modulated 50 of the 53 identified DEGs.
• This combination demonstrated multifaceted effects on pathways including inflammation, cell proliferation, autophagy, apoptosis, angiogenesis, and metastasis.

Conclusions:

• The identified compound combination effectively targets key genes driving prostate cancer progression and treatment resistance.
• This natural compound concoction shows potential for developing enhanced immunotherapeutics and combinatorial treatments for PCa.
• The findings suggest a novel strategy to overcome immune evasion and impede treatment resistance in prostate tumors.