Molecular Prioritization of Gene Therapy Targets in Skin Cancer Using the MEREC–VIKOR Multi-Criteria Decision-Making Approach
Keywords
Melanoma gene therapy, Multi-criteria decision-making, Translational oncogenomic, Precision medicine, MEREC–VIKOR method
Abstract
Despite significant advances in oncogenomics, the development of gene therapy for melanoma continues to face a high rate of translational failure due to its reliance on single-dimensional criteria, such as mutation frequency, while overlooking critical technical and safety-related challenges. The objective of this study was to develop a systematic Multi-Criteria Decision-Making (MCDM) framework for the optimal prioritization of therapeutic targets by balancing biological potential with practical and operational considerations. In this study, 20 candidate genes, including oncogenic drivers, tumor suppressor genes, and immune-related factors, were evaluated based on 10 key criteria, including functional significance, compatibility with gene delivery vectors, drugability, and immunological safety profiles. By integrating the Method based on the Removal Effects of Criteria (MEREC) method for objective weighting and minimizing subjective bias with the VlseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method for compromise ranking, a comprehensive framework was established for prioritizing therapeutic gene targets. The findings revealed that NRAS, STAT3, and TP53 achieved the highest rankings and emerged as the most promising therapeutic candidates. The consistency of these priorities with previous studies supports the scientific validity of the proposed framework. However, the primary contribution of this research lies in its ability to systematically identify candidate targets that not only possess high therapeutic potential but also present the lowest levels of technical complexity and safety risks for gene delivery. Notably, the proposed approach appropriately assigned clinically important but technologically challenging targets, such as PD-L1, to secondary priority levels, demonstrating its effectiveness in balancing clinical relevance against practical implementation constraints. By moving beyond conventional target-selection paradigms, this framework provides a strategic tool for precision medicine, enabling research resources to be directed toward therapeutic targets with the greatest likelihood of successful clinical translation rather than high-risk exploratory approaches. Furthermore, the proposed methodology offers a reproducible roadmap for translational oncogenomics. It establishes a robust foundation for future in vivo studies aimed at developing the next generation of safe and effective gene therapies for melanoma.
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