Future perspectives of personalized oncology

Abstract

Based upon an individual's molecular make-up, personalized molecular medicine provides information regarding the origin of disease, its treatment and progression, while personalized molecular pharmacology advises on drug prescription and patient response to it, thus ensuring drug effectiveness and preventing drug toxicity or lack of response. Interindividual differences in drug responses are mostly due to structural variation in parts of genome, e.g. in genes participating in drug metabolism, transport or targeting. However, a wide variety of diseases and accompanying health conditions, including patient's therapy or drug response, also have epigenetic or epigenomic etiology. High priority for personalized oncologic research stems from inter/intraindividual tumor heterogeneity provoked by gradual acquisition of multiple random, or programmed mutations and rearrangements as well as epigenetic alterations or by stochastic fluctuations in cell components, all in tight feedback interaction with tumor's environmental or therapy conditions. Natural selection subsequently shapes inter/intraindividual tumor heterogeneity by promoting clonal expansion of cells that have acquired advantageous mutations for tumor population. Hence, the main rationale of personalized molecular oncology should focus on treating disease by relying on relevant structure and state of patient's whole molecular network (genome/transcriptome/RNome/proteome/metabolome/metabonome) in interaction with its unique environmental conditions, thus implying right therapy for the right patient at the right dose and time. The future of personalized oncology should therefore rely on the methods of systems biology applied in cytology and pathology in order to develop and utilize the efficient and effective diagnostic, prognostic and predictive biomarkers, consequently providing the molecular information on tumor origin, its potential for metastasis, adequate therapy, tumor specific therapy responsiveness, and the probability of its recurrence.