TLDR Targeting the Smoothened receptor shows promise for treating certain cancers.
The document reviewed the therapeutic potential of targeting the Smoothened (Smo) receptor, a key component of the Hedgehog (Hh) signaling pathway, for cancer treatment. Smo antagonists showed promise in treating Hh-linked cancers, with vismodegib being approved for metastatic basal cell carcinoma. Smo agonists were also important for understanding both canonical and noncanonical Hh signaling. The review highlighted the complexity of Smo pharmacology, including its three-dimensional structure and multiple ligand-binding sites, which could inform the design of new therapeutic agents. Noncanonical Hh signaling mechanisms, such as those involving Src kinase activation and Ca2+ spikes, were also discussed.
136 citations,
April 2013 in “Clinical Cancer Research” The drug IPI-926 is safe at 160 mg daily and may help treat certain tumors, especially basal cell carcinoma.
21 citations,
November 2021 in “Cells” Hedgehog pathway inhibitors can treat certain aggressive cancers but face limitations like resistance and side effects.
15 citations,
October 2014 in “Journal of Investigative Dermatology” New treatments targeting the Hedgehog pathway can help treat advanced skin cancer but may have side effects and their effectiveness in early stages is unknown.
127 citations,
August 2016 in “The oncologist” Understanding and managing side effects of hedgehog pathway inhibitors can improve treatment for advanced basal cell carcinoma.
9 citations,
December 2014 in “British Journal of Dermatology” Hedgehog pathway inhibitors used for skin cancer can cause significant hair loss, which may improve after stopping the medication.
16 citations,
March 2015 in “Clinical Cancer Research” The document concludes that side effects from Smoothened inhibitor drugs for skin cancer are reversible and can be managed with a team approach to maintain quality of life.
