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Updated: May 8, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
New developments in dermatological oncogenetics
1Department of Dermatology, Venereology and Allergology, University of Leipzig, Germany.
Abstract:
Activated intracellular signaling pathways based on mutations in oncogenes and tumor suppressor genes play an important role in a variety of malignant tumors. In dermatology, such mutations have been identified in melanoma, basal cell carcinoma and squamous cell carcinoma. These have partly led to the establishment of new, targeted therapies. Treatment successes have been particularly impressive for melanoma with small molecule inhibitors directed against the mutated BRAF oncogene and in basal cell carcinoma with inhibitors directed against the hedgehog signaling pathway. New sequencing technologies, in particular next generation sequencing, have led to a better and more comprehensive understanding of malignant tumors. This approach confirmed the pathogenic role of BRAF, NRAS and MAP kinase pathways for melanoma. At the same time, a series of further interesting target molecules with oncogenic mutations such as ERBB4, GRIN2A, GRM3, PREX2, RAC1 and TP53 were identified. New aspects have recently been shown for squamous cell carcinoma by detection of mutations in the NOTCH signaling pathway. A better understanding of the pathogenesis of these and other tumors should lead to improved and maybe even individualized treatment. The current developments in dermatological oncogenetics based on the new sequencing technologies are reviewed.
Insights
Targeted therapies for skin cancers like melanoma and basal cell carcinoma are advancing due to understanding oncogene mutations. Next-generation sequencing aids in identifying new targets for improved dermatological cancer treatment.
Area of Science:
- Dermatological oncology
- Cancer genetics
- Molecular biology
Background:
- Mutations in oncogenes and tumor suppressor genes activate intracellular signaling pathways crucial in malignant tumors.
- Dermatological malignancies such as melanoma, basal cell carcinoma, and squamous cell carcinoma harbor specific mutations.
- Targeted therapies have emerged, showing significant success, particularly in melanoma and basal cell carcinoma.
Purpose of the Study:
- To review current developments in dermatological oncogenetics.
- To highlight the impact of new sequencing technologies on understanding skin cancer pathogenesis.
- To discuss the identification of novel molecular targets for improved cancer treatment.
Main Methods:
- Review of current literature on dermatological oncogenetics.
- Analysis of findings from next-generation sequencing studies.
- Identification of key signaling pathways and mutated genes in skin cancers.
Main Results:
- BRAF, NRAS, and MAP kinase pathways are confirmed as pathogenic drivers in melanoma.
- Targeted therapies against BRAF (melanoma) and hedgehog pathway (basal cell carcinoma) demonstrate impressive treatment success.
- New oncogenic mutations in ERBB4, GRIN2A, GRM3, PREX2, RAC1, TP53, and the NOTCH pathway (squamous cell carcinoma) have been identified.
Conclusions:
- Next-generation sequencing significantly enhances the understanding of malignant tumor biology.
- Identification of novel oncogenic mutations paves the way for new targeted and potentially individualized therapies in dermatology.
- Advances in oncogenetics promise improved treatment strategies for skin cancers.
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