Thérapies ciblées et carcinomes basocellulaires

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• 作者：N. Basset-Seguin (12259)
  
• 关键词：Targeted therapy ; Advanced basal cell carcinoma ; Metastatic basal cell carcinoma ; Treatment ; Thérapie ciblée ; Carcinomes basocellulaires avancés ; Carcinomes basocellulaires métastatiques ; Traitement
• 刊名：Oncologie
• 出版年：2013
• 出版时间：February 2013
• 年：2013
• 卷：15
• 期：2
• 页码：101-105
• 全文大小：225KB
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  14. Skvara H, Kalthoff F, Meingassner JG, et al. (2011) Topical treatment of basal-cel carcinomas in nevoid basal-cell carcinoma syndrome with a smoothened inhibitor. J Invest Dermatol 131(8): 1735-744. doi: 10.1038/jid.2011.48. p://dx.doi.org/10.1038/jid.2011.48">CrossRef
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  16. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. (2012) Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med 366(23): 2180-188 p://dx.doi.org/10.1056/NEJMoa1113538">CrossRef
  17. Tang JY, Xiao TZ, Oda Y, et al. (2011) Vitamin D3 inhibits hedgehog signaling and proliferation in murine basal-cell carcinomas. Cancer Prev Res (Phila) 4(5): 744-51 p://dx.doi.org/10.1158/1940-6207.CAPR-10-0285">CrossRef
  18. Tang T, Tang JY, Li D, et al. (2011) Targeting superficial or nodular basal-cell carcinoma with topically formulated small molecule inhibitor of smoothened. Clin Cancer Res 17(10): 3378-387 p://dx.doi.org/10.1158/1078-0432.CCR-10-3370">CrossRef
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  20. Von Hoff DD, LoRusso PM, Rudin CM, et al. (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361(12): 1164-172 p://dx.doi.org/10.1056/NEJMoa0905360">CrossRef
  
• 作者单位：N. Basset-Seguin (12259)
  
  12259. H?pital Saint-Louis, 1, avenue Claude-Vellefaux, F-75010, Paris, France
  

文摘

Basal cell carcinomas (BCCs) are the most frequent cancers in fair-skin adult patients. While most of them are accessible to medical or surgical treatment, some rare locally destructive forms (so called locally advanced BCC or someexceptionalmetastatic forms) cannot be treated by surgery or radiotherapy. Conventional chemotherapy (cisplatin, doxorubicine) is often difficult to perform as it is mostly palliative and not well tolerated in elderly patients. In 1996, the molecular pathway involved in BCC formation was identified: the patch/sonic/hedgehog pathway. Since then, major efforts have been performed to develop a targeted therapy to control the abnormal activation of the pathway. In 2009, results of the first phase I study were published using an anti-smo: the GDC-449 or vismodegib showing tolerability and anti-tumoral efficacy of this product. Response rates around 50% for both locally advanced and metastatic BCC have been obtained which were never achieved before. Since then several phase II studies have confirmed the efficacy of anti-smo molecules and extended their trial in the high risk for BCC Gorlin syndrome for multiple operable BCC. Long-termtolerability for these molecules is still not optimal andmust be improved. Targeted anti-smo molecule dramatically changes the strategy of care of patients with locally advanced ormetastatic BCC. In early 2012, vismodegib was approved by the FDA for the treatment of locally advanced or metastatic BCC.