L Boeckmann1, M C Martens2, V Kakkassery3, L M Heindl4,5, S Emmert6. 1. Klinik und Poliklinik für Dermatologie und Venerologie, Universitätsmedizin Rostock, Strempelstr. 13, 18057, Rostock, Deutschland. Lars.Boeckmann@med.uni-rostock.de. 2. Klinik und Poliklinik für Dermatologie und Venerologie, Universitätsmedizin Rostock, Strempelstr. 13, 18057, Rostock, Deutschland. 3. Klinik für Augenheilkunde, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Deutschland. 4. Zentrum für Augenheilkunde, Universität zu Köln, Köln, Deutschland. 5. Centrum für Integrierte Onkologie (CIO) Aachen - Bonn - Cologne - Düsseldorf, Köln, Deutschland. 6. Klinik und Poliklinik für Dermatologie und Venerologie, Universitätsmedizin Rostock, Strempelstr. 13, 18057, Rostock, Deutschland. steffen.emmert@med.uni-rostock.de.
Abstract
BACKGROUND: Basal cell carcinomas are generally the most common malignant human cancers. They grow destructively and invasively into surrounding tissue. OBJECTIVE: The rising incidence of basal cell carcinomas in an aging society demands new, less destructive treatment approaches especially for advanced and difficult to resect basal cell carcinomas at surgically demanding locations, such as those growing or metastasizing on the eyelid. MATERIAL AND METHODS: New key technologies, such as next generation sequencing (NGS) enable high-throughput genetic analyses of tumors. In this way new knowledge on the molecular genetic pathogenesis of basal cell carcinomas is gained, which enables the development of new targeted treatment of the affected signal pathway. RESULTS: In line with the multistep photocarcinogenesis theory, basal cell carcinomas possess a high load of UV-induced gene mutations (75%). Independent of the genesis 85% of basal cell carcinomas harbor activating mutations of the hedgehog signaling pathway. Accordingly, two hedgehog inhibitors for the treatment of difficult to resect or metastasized basal cell carcinomas have been licensed (vismodegib and sonidegib); however, only 60% of patients respond to this treatment. This is due to the high mutational load with 85% of the tumors harboring additional mutations in other signaling pathways. CONCLUSION: Molecular genetic analyses will enable the identification of further targeted therapies for advanced basal cell carcinomas. Due to the high mutational load checkpoint inhibitors (e. g. cemiplimab) are also effective in the treatment of basal cell carcinomas. Nicotinamide and UV protection can reduce the mutational load and hence decrease the risk for tumor development.
BACKGROUND:Basal cell carcinomas are generally the most common malignant humancancers. They grow destructively and invasively into surrounding tissue. OBJECTIVE: The rising incidence of basal cell carcinomas in an aging society demands new, less destructive treatment approaches especially for advanced and difficult to resect basal cell carcinomas at surgically demanding locations, such as those growing or metastasizing on the eyelid. MATERIAL AND METHODS: New key technologies, such as next generation sequencing (NGS) enable high-throughput genetic analyses of tumors. In this way new knowledge on the molecular genetic pathogenesis of basal cell carcinomas is gained, which enables the development of new targeted treatment of the affected signal pathway. RESULTS: In line with the multistep photocarcinogenesis theory, basal cell carcinomas possess a high load of UV-induced gene mutations (75%). Independent of the genesis 85% of basal cell carcinomas harbor activating mutations of the hedgehog signaling pathway. Accordingly, two hedgehog inhibitors for the treatment of difficult to resect or metastasized basal cell carcinomas have been licensed (vismodegib and sonidegib); however, only 60% of patients respond to this treatment. This is due to the high mutational load with 85% of the tumors harboring additional mutations in other signaling pathways. CONCLUSION: Molecular genetic analyses will enable the identification of further targeted therapies for advanced basal cell carcinomas. Due to the high mutational load checkpoint inhibitors (e. g. cemiplimab) are also effective in the treatment of basal cell carcinomas. Nicotinamide and UV protection can reduce the mutational load and hence decrease the risk for tumor development.
Authors: Aleksandar Sekulic; Michael R Migden; Anthony E Oro; Luc Dirix; Karl D Lewis; John D Hainsworth; James A Solomon; Simon Yoo; Sarah T Arron; Philip A Friedlander; Ellen Marmur; Charles M Rudin; Anne Lynn S Chang; Jennifer A Low; Howard M Mackey; Robert L Yauch; Richard A Graham; Josina C Reddy; Axel Hauschild Journal: N Engl J Med Date: 2012-06-07 Impact factor: 91.245
Authors: Mohammad Athar; Changzhao Li; Arianna L Kim; Vladimir S Spiegelman; David R Bickers Journal: Cancer Res Date: 2014-08-29 Impact factor: 12.701
Authors: Vinodh Kakkassery; Steffen Emmert; Irenäus A Adamietz; György Kovács; Anselm M Jünemann; Caroline Otte; Michael Zimbelmann; Anton Brosig; Salvatore Grisanti; Ludwig M Heindl Journal: Ophthalmologe Date: 2020-02 Impact factor: 1.059