Current approaches and strategies to identify Hedgehog signaling pathway inhibitors for cancer therapy

Area of Science:

• Biochemistry
• Oncology
• Drug Discovery

Background:

• The Hedgehog signaling pathway is essential for embryonic development and tissue patterning.
• Dysregulation of this pathway is linked to various cancers, making it a therapeutic target.
• Approved Hedgehog pathway inhibitors (Vismodegib, Sonidegib, Glasdegib) show promise but have limitations.

Purpose of the Study:

• To provide a comprehensive overview of current strategies for developing Hedgehog pathway inhibitors.
• To discuss the characteristics and challenges associated with different inhibitor development approaches.
• To explore future prospects for next-generation Hedgehog pathway inhibitors.

Main Methods:

• Systematic review of various inhibitor development approaches.
• Analysis of library screening, natural product-oriented methods, analogue design, drug repositioning, and in silico tools.
• Discussion of existing and emerging therapeutic strategies.

Main Results:

• Several methods are employed for developing Hedgehog pathway inhibitors, including screening, natural products, analogue design, drug repositioning, and computational tools.
• Existing drugs face clinical hurdles like adverse effects and resistance.
• Diverse approaches are being explored to overcome these limitations.

Conclusions:

• The development of novel Hedgehog pathway inhibitors is critical due to limitations of current therapies.
• A systematic overview reveals various strategies and future directions for next-generation inhibitor discovery.
• Continued research into diverse approaches is essential for advancing cancer treatment.