From sympathetic overdrive phenotype to malignant transformation: 3PM-guided protection against health-to-disease transition and disease progression improving individual outcomes in primary and secondary care.

Chronic sympathoexcitation (sympathetic overdrive syndrome) is defined as the sustained dominance of sympathetic over parasympathetic tone, measurable at the organ, vascular, and neural levels, and differs fundamentally from brief, adaptive "fight-or-flight" responses. Persistent vasoconstrictor drive perturbs cellular metabolism and reshapes host-tumor interfaces. Although this state is well characterized in cardiometabolic medicine, its oncologic implications remain comparatively underexplored, despite converging evidence that adrenergic inputs modulate tumor and stromal behavior. One of the main reasons for presenting this conceptual innovation study is that the sympathetic overdrive phenotype (SOP) carriers, by far, are not rare in the population. Robust statistics towards SOP incidence and prevalence are still missing, despite the urgency of plausible healthcare solutions. Currently, the best described SOP-relevant subpopulation are the Flammer Syndrome phenotype (FSP) carriers who, for instance, are highly prevalent in the academic career-making professional groups. Certain genetic predispositions play a role, however, the key pathways involved into the health-to-disease transition are epigenetically regulated and, to a large extent, represent systemic modifiable phenotype-associated risk factors which are, therefore, a promising target for holistic proactive medical approaches with a high potential to save lives and financial resources. Graphical Abstract: