title: Vismodegib, itraconazole and sonidegib as hedgehog pathway inhibitors and their relative competencies in the treatment of basal cell carcinomas.
abstract: The advent of more sophisticated studies published has clarified the understating of the root cause of various skin cancers or basal cell carcinomas (BCCs). The remarkable role is played by the comprehensive work done on unraveling the mechanism controlling the function of hedgehog (Hh) pathway. The defective Hh pathway has been found as the major cause for BCCs as activated Hh signaling within primary cilia plays a key role in the pathogenesis of BCCs. The BCC accounts for up to 40% of all cancers in the US, with growing incidences in other countries as well. Thus, it is considered to be utmost important by the researchers all over the world developing drugs for the treatment of skin cancers targeting Hh pathway. Fewer drugs like vismodegib, itraconazole and sonidegib have shown promising results inhibiting the awry function of Hh pathway resulting in treatment of different forms of skin cancers. These drugs have shown positive results but failed to prove their potential as expected. Vismodegib and sonidegib are better but fail in case of resistant tumors. This review article describes the mechanism of actions of these Hh pathway inhibitors and provides the rationale for their effectiveness/non-effectiveness for the treatment of metastatic or locally advanced BCC.
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University), New Delhi 110025, India; Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia.
authors.forename: Mohd
authors.initials: M
authors.lastname: Wahid
authors.affiliation: GE Healthcare, Sector-43, Gurgaon 122002, Haryana, India.
authors.forename: Arshad
authors.initials: A
authors.lastname: Jawed
authors.affiliation: Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow 226014, UP, India.
authors.forename: Raju K
authors.initials: RK
authors.lastname: Mandal
authors.affiliation: Division of Gynecology Oncology, Women's Health Services, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Sajad A
authors.initials: SA
authors.lastname: Dar
authors.affiliation: Department of Biosciences, Integral University, Lucknow 226026, UP, India.
authors.forename: Saif
authors.initials: S
authors.lastname: Khan
authors.affiliation: Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Naseem
authors.initials: N
authors.lastname: Akhter
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; Centre for Drug Research, Faculty of Pharmacy, Viikki Biocentre-2, University of Helsinki, Helsinki FI-00014, Finland. Electronic address: shafiul.haque@hotmail.com.
authors.forename: Shafiul
authors.initials: S
authors.lastname: Haque
mesh_terms: D000813:Anilides / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage; D002280:Basal Cell Carcinoma / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000813:Anilides; D001713:Biphenyl Compounds; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines; C561435:sonidegib; D017964:Itraconazole
keywords: Basal cell carcinoma; Hedgehog pathway; Itraconazole; Metastasis; Sonidegib; Vismodegib