TLDR 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.
The document reviewed the role of Hedgehog (Hh) signaling in the pathogenesis of basal cell carcinoma (BCC) and the development of targeted therapeutics, such as vismodegib, to inhibit this pathway. It discussed the genetic mutations, particularly in the PTCH1 gene, that predispose individuals to BCC and the effectiveness of Hh pathway inhibitors in treating locally advanced and metastatic BCC, with response rates of 43% and 30% respectively. The review also mentioned the potential for drug resistance and side effects like muscle cramps and alopecia. While Hh pathway inhibitors represent a significant advancement in treating advanced BCC, their effectiveness in less advanced cases or as a preventative treatment is still uncertain, and further research is needed to understand and mitigate the side effects of these drugs.
63 citations,
May 2011 in “Clinical cancer research” The topical inhibitor CUR61414 was not effective in treating basal cell carcinoma in human trials.
351 citations,
February 2010 in “Nature Cell Biology” Basal cell carcinoma mostly starts from cells in the upper skin layers, not hair follicle stem cells.
194 citations,
May 2000 in “Journal of Investigative Dermatology” The hedgehog signaling pathway is crucial for hair growth but not for the initial creation of hair follicles.
68 citations,
November 2011 in “The American journal of pathology” Abnormal Hedgehog signaling in blood cancers may help tumors grow and resist chemotherapy, suggesting potential for targeted treatments.
105 citations,
April 2014 in “Trends in Pharmacological Sciences” Targeting the Smoothened receptor shows promise for treating certain cancers.
8 citations,
May 2019 in “Journal of dermatological treatment” Vismodegib is effective for basal cell carcinoma but has severe side effects.
17 citations,
June 2017 in “British Journal of Dermatology” The article concludes that hair loss is a common side effect of drugs treating skin cancer by blocking the hedgehog pathway, but treatment should continue, and more selective drugs might prevent this side effect.
72 citations,
November 2017 in “Journal of developmental biology” The Hedgehog signaling pathway is important for skin and hair growth and can lead to cancer if it doesn't work right.
