title: Implementation of Systemic Hedgehog Inhibitors in Daily Practice as Neoadjuvant Therapy.
abstract: The most common cancer in both men and women is basal cell carcinoma (BCC). Although most primary and recurrent BCCs have high cure rates with standard therapies, advanced BCCs present a greater treatment challenge, especially in cosmetically and functionally sensitive areas. In patients unable to undergo surgery or radiation therapy, hedgehog inhibitors can be used neoadjuvantly to reduce tumor size, decreasing the extent and complexity of any subsequent surgery and providing either a cure or palliation. The goal of this review is to summarize the pharmacology, efficacy, and safety of systemic hedgehog inhibitors, as well as their role in daily practice as neoadjuvant therapy. Relevant English-language literature was identified and evaluated based on results from database searches of PubMed. Terms searched included, but were not limited to, "vismodegib," "Erivedge," "sonidegib," "DE225," "BCC," and "neoadjuvant treatment." Additional literature was identified from the reference lists of previously identified articles. The authors' personal experience in treating advanced BCC using hedgehog inhibitors has been incorporated into the recommendations made herein.
authors.affiliation: From Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
authors.forename: Nikki
authors.initials: N
authors.lastname: Tang
authors.affiliation: Comprehensive Skin Cancer Center, Icahn School of Medicine at Mount Sinai and Mount Sinai Beth Israel Medical Center, New York, New York
authors.forename: Desiree
authors.initials: D
authors.lastname: Ratner
mesh_terms: D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D059039:Standard of Care; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines; C561435:sonidegib