Dual HDAC/PI3K inhibitors as a potential and emerging cancer therapy: a review

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Cancer's heterogeneity drives uncontrolled growth and therapeutic evasion.
• Histone Deacetylases (HDACs) and Phosphoinositide 3-kinases (PI3Ks) are critical regulators of cell survival, proliferation, and epigenetic processes.
• Dysregulation of HDAC and PI3K pathways contributes to tumor initiation, progression, and treatment resistance.

Purpose of the Study:

• To review the biological roles, chemical properties, and structure-activity relationships (SAR) of HDAC and PI3K family members.
• To explore dual HDAC/PI3K inhibition as a unified therapeutic approach for cancer.
• To discuss the potential of dual inhibitors in treating diverse cancers and future clinical directions.

Main Methods:

• Comprehensive review of literature on HDAC and PI3K pathways and inhibitors.
• Analysis of chemical structures and SAR of FDA-approved HDAC, PI3K, and dual inhibitors.
• Discussion of clinical trial data and future research avenues for dual HDAC/PI3K inhibitors.

Main Results:

• HDAC and PI3K pathways are key targets in cancer due to their roles in epigenetic regulation and cell signaling.
• Dual HDAC/PI3K inhibitors, like CUDC-907 and BEBT-908, offer a simultaneous approach to inhibit these critical pathways.
• These dual inhibitors demonstrate potential efficacy in both cytogenetic cancers and solid tumors.

Conclusions:

• Dual HDAC/PI3K inhibition represents a promising next-generation anticancer strategy.
• This approach effectively targets multiple cancer-driving mechanisms, overcoming limitations of single-target therapies.
• Further clinical investigation is warranted to optimize therapeutic outcomes and expand the application of dual inhibitors.