What a clinician needs to know about modern concepts of the development and progression of malignant tumors?

The traditional paradigm, which considers cancer exclusively as a genetic disease caused by somatic mutations, is currently evolving towards a multifactorial model. This paper analyzes current data on the relationship between the genetic, epigenetic, and metabolic mechanisms of oncogenesis. Despite the key role of driver mutations in genes such as TP53, KRAS, and PIK3CA, it is now becoming clear that their presence is insufficient for malignant transformation. Epigenetic deregulation and metabolic reprogramming play an important role even in the absence of significant genetic changes.
The existence of a «three-way network» is becoming apparent, where genetic, metabolic, and epigenetic pathways mutually reinforce each other, ensuring tumor plasticity and resistance to treatment. It is important for clinical practice to understand that influencing a single node of this network is often ineffective due to compensatory adaptation. Thus, complex molecular profiling and the development of rational combined treatment regimens are necessary, simultaneously affecting several links of pathogenesis in order to overcome resistance and personalize therapy.