[Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing]

Area of Science:

• Oncology
• Dermatology
• Molecular Diagnostics

Background:

• Malignant melanoma, a rare but aggressive skin cancer, exhibits diverse etiopathogenesis, behavior, and prognosis.
• Recent findings reveal melanoma as a spectrum of neoplasms, necessitating refined diagnostic and therapeutic approaches.
• Targeted therapies blocking the MAPK signaling pathway require BRAF mutation testing for patient selection.

Purpose of the Study:

• To correlate morphological findings with genetic alterations in malignant melanoma.
• To discuss the proposed genetic classification, BRAF testing challenges, and its status in the Czech Republic.
• To explore limitations of BRAF/MEK targeted therapy due to tumor heterogeneity and acquired resistance.

Main Methods:

• Review and summarization of current literature on melanoma genetics and diagnostics.
• Analysis of BRAF mutation testing methods, prevalence, and future trends.
• Discussion of acquired resistance mechanisms and combination therapy strategies.

Main Results:

• Malignant melanoma comprises diverse genetic subtypes impacting prognosis and treatment response.
• BRAF testing is essential for identifying patients eligible for MAPK pathway-targeted therapies.
• Tumor heterogeneity and acquired resistance pose significant challenges to targeted treatment efficacy.

Conclusions:

• Accurate genetic classification and BRAF testing are vital for personalized melanoma treatment.
• Addressing tumor heterogeneity and resistance mechanisms is critical for improving therapeutic outcomes.
• Future research should focus on combination therapies, including immunotherapy, to overcome treatment limitations.