Hedgehog signaling inhibitors in solid and hematological cancers

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The hedgehog signaling pathway is crucial in development but its aberrant activation drives cancer.
• Mutations in hedgehog pathway components can lead to uncontrolled cell growth.
• Hedgehog inhibitors (HHIs) are emerging as targeted therapies for various cancers.

Purpose of the Study:

• To review known hedgehog inhibitors (HHIs).
• To explore the potential of HHIs in treating hematological cancers and solid tumors beyond basal cell carcinoma (BCC).

Main Methods:

• Literature search for preclinical and clinical studies on HHIs in non-cutaneous cancers.
• Inclusion of relevant clinical trial data from clinicaltrials.gov.
• Inclusion of pharmacological information on HHIs.

Main Results:

• HHIs demonstrate efficacy in preclinical models of pancreatic cancer, rhabdomyosarcoma, breast cancer, and acute myeloid leukemia (AML).
• Clinical studies show HHI activity in medulloblastoma, prostate cancer, pancreatic cancer, and hematological malignancies.
• Ongoing clinical trials are evaluating HHIs for prostate, pancreatic, breast cancers, multiple myeloma, and AML.

Conclusions:

• Clinical trial outcomes will identify additional tumor types responsive to HHI monotherapy or combination therapy.
• Combination strategies may prove effective in delaying or overcoming acquired drug resistance.
• HHIs represent a promising therapeutic avenue for a range of difficult-to-treat cancers.