Personalization of medical treatments in oncology: time for rethinking the disease concept to improve individual outcomes

AbstractThe agenda of pharmacology discovery in the field of personalized oncology was dictated by the search of molecular targets assumed to deterministically drive tumor development. In this perspective, genes play a fundamental “causal” role while cells simply act as causal proxies, i.e., an intermediate between the molecular input and the organismal output. However, the ceaseless genomic change occurring across time within the same primary and metastatic tumor has broken the hope of a personalized treatment based only upon genomic fingerprint. Indeed, current models are unable in capturing the unfathomable complexity behind the outbreak of a disease, as they discard the contribution of non-genetic factors, environment constraints, and the interplay among different tiers of organization. Herein, we posit that a c omprehensive personalized model should view at the disease as a “historical” process, in which different spatially and timely distributed factors interact with each other across multiple levels of organization, which collectively interact with a dynamic gene-expression pattern. Given that a dise ase is a dynamic, non-linear process — and not a static-stable condition — treatments should be tailored according to the “timing-frame” of each condition. This approach can help in detecting those critical transitions through which the system can access different attractors leading ultimate ly to diverse outcomes — from a pre-disease state to an overt il...
Source: EPMA Journal - Category: International Medicine & Public Health Source Type: research