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

The 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 comprehensive 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 disease 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 ultimately to diverse outcomes - from a pre-disease state to an overt illness or, alternatively, to recovery. Identification of such tipping points can substantiate the predictive and the preventive ambition of the Predictive, Preventive and Personalized Medicine (PPPM/3PM). However, an unusual effort is required to conjugate multi-omics approaches, data collection, and network analysis reconstruction (eventually involving innovative Artificial Intelligent tools) to recognize the critical phases and the relevant targets, which could help in patient stratification and therapy personalization.

Automated summary

Current models of personalized oncology treatment based solely on genomic factors overlook the complexity and dynamic nature of diseases, leading to the need for a comprehensive personalized model that considers diseases as historical processes influenced by various factors interacting across different levels of organization and dynamic gene-expression patterns. Treatment strategies should be tailored based on the timing of each condition to detect critical transitions that can ultimately lead to different outcomes, from pre-disease states to recovery, requiring a concerted effort in multi-omics approaches, data collection, network analysis, and utilization of innovative AI tools for patient stratification and therapy personalization.