Christian Leonardo Valencia Eraso

Precision oncology has traditionally focused on genomic profiling to guide targeted therapies; however, increasing evidence suggests that genetic alterations alone are insufficient to fully explain tumor behavior, therapeutic response, and clinical heterogeneity. This review aims to analyze precision oncology beyond genetics by integrating metabolic flexibility, tumor microenvironment dynamics, immune profiling, and systemic physiological factors, with particular emphasis on dermatology and internal medicine in international contexts, including Mexico, Colombia, and Ecuador. A structured narrative review was conducted using the scientific method as a guiding framework, allowing for the systematic identification, analysis, and integration of relevant literature. The findings demonstrate that tumor metabolism, particularly metabolic flexibility, plays a central role in adaptation and resistance. Additionally, the tumor microenvironment and immune profiling are critical determinants of treatment response, especially in the context of immunotherapy. The concept of the kidney as a sensor organ highlights the importance of systemic physiology in oncologic outcomes, particularly regarding drug clearance, toxicity, and metabolic balance. Furthermore, cardiometabolic conditions such as obesity, diabetes, and chronic inflammation significantly influence tumor progression and therapeutic effectiveness. The integration of these dimensions supports a systems-based model of precision oncology, where tumor biology and host factors interact dynamically. This approach is particularly relevant for dermatology and internal medicine, as it allows for a more comprehensive understanding of both local and systemic disease processes. In addition, the proposed framework offers practical applicability in diverse healthcare settings, including regions with limited access to advanced molecular technologies.