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Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond
Author(s) -
Bakshi Anshika,
Chaudhary Sandeep C.,
Rana Mehtab,
Elmets Craig A.,
Athar Mohammad
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22690
Subject(s) - biology , pathogenesis , basal cell carcinoma , hedgehog signaling pathway , hedgehog , cancer research , basal (medicine) , microbiology and biotechnology , signal transduction , basal cell , immunology , medicine , endocrinology , insulin
Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling‐related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10‐100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug‐binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent‐based or multiple agents‐based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs.