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Authors:  Sergey Suchkov^1-6,10, Daniel Scherman¹⁰, Veronika Polyakova^13, Shawn Murphy^7,8, David Smith^11, Valentina Demidova^14, Lidiya Kadyrova^18, Mark Hendrikx^8, Vladimir Zemskov^14, Michael J. Duffy^14-16, Hiroyuki Abe^5,9, R. Holland Cheng¹² 

1. The Russian Academy of Natural Sciences, Moscow, Russia
2. Department for Clinical Allergology & Immunology, The Russian University of Medicine, Moscow, Russia
3. EPMA, Brussels, EU
4. PMC, Washington, DC, USA
6. ISPM, Tokyo, Japan
5. New York Academy of Sciences, USA
6. MGH, Boston, MA, USA
7. Harvard Medical School, Boston, MA, USA
8. Abe Cancer Clinic, Tokyo, Japan
9. The University of World Politics and Law, Moscow, Russia
10. Centre de Recherche Pharmaceutique de Paris (CRP2); Faculté de Pharmacie, Université Paris Descarte, Paris, France
11. Mayo Clinic, Rochester, MN, USA
12. College of Biological Sciences, University of California Davis, Davis, CA, USA
13. University of World Politics & Law, Moscow, Russia
14. National Medical Research Center for Surgery named after A.V. Vishnevsky, Moscow, Russia
15. Department of Pathology and Laboratory Medicine, University College Dublin, Dublin, Ireland
16. Dublin Molecular Medicine Institute, University College Dublin, Dublin, Ireland
17. UCD School of Medicine and Medical Science of the Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland

Abbrevations:
PPM - Personalized & Precision Medicine, CHD - coronary heart disease, CAD - coronary artery disease, SNPs - Single Nucleotide Polymorphisms, CVD - cardiovascular diseases, CDS - Clini-cal decision support, CTCs - circulating tumor cells, CSCs - cancer stem cells.

INTRODUCTION:
Throughout its history, medicine and healthcare philosophy have paid special attention to already-diseased individuals, focusing on clinically manifested diseases (nosology) instead of one’s health or so-called pre-illness conditions. The latter are left in the shade, while the former have been overlooked. This is a fact based on evidence. Therefore, clinical efficacy, chronicity, disability rates, and human longevity need to be drastically improved in the near future. While analyzing and preselecting the basic determinants of health (Fig. 1).To be valuable for implementing and securing the effectiveness of the upgraded healthcare model in daily clinical practice, a group of recognized experts presented an evidence-based and well-documented assessment of global trends in medicine and healthcare develop-ment. They emphasized the exclusive value of Personalized & Precision Medicine (PPM), which is the next step in healthcare service delivery (Fig. 2). Precision medicine identifies differences between individuals, categorizing them based on environmental, biological, and psychosocial fac-tors. Personalized medicine uses these differences to implement preventions and treatments tai-lored to each individual. This approach alters the current treatment model, shifting focus towards identifying potential drug targets, real-time monitoring of patients’ health, effective early detec-tion of disease, identification of genes causing diseases, phenotypic and genetic heterogeneity, and also altering the role of doctors.PPM refers to tailoring diagnostics or therapeutics to individual patients based on their unique genetic and physiological characteristics. Personalized medicine takes into account these differences and provides tailored preventions/treatments. Precision medicine identifies variations in environmental, biological, and psychological factors among individuals and develops tailored treatment strategies. PPM is one of the most promising approaches for tackling diseases that have so far elud-ed effective treatments. An example of personalized care is using biomarkers and targets to bet-ter define disease subtypes, prognosis, or inform therapy decisions. Regarding cancer, PPM often means considering how changes in genes or proteins within a person’s cancer cells could affect their care, including their treatment options. Precision medicine has the potential to further personalize care in the future. To achieve further improvements in health care, progress in all of these areas needs to continue. This is true not only for OMICS-based PPM, but also for other aspects of health care [1, 2]. PPM as a model of healthcare services for the next generation is the application of science and art, illustrating the use of different tools from the model at population, community and indi-vidual levels. It has its roots in traditional medicine and has passed on to stratified medicine, and finally gave rise to PPM. It exerts reliable control over morbidity, mortality, disabling rates, as well as optimizing the cost and effectiveness of treatment for patients and at-risk persons. This strategy provides a real opportunity for preventive, prophylactic, therapeutic, and rehabilitative measures, whose personalization can have a significant positive impact on demographics. Person-alized treatment is therefore becoming a core goal of the medical field,and PPM in particular. In this context, each decision-maker values the impact of their decision to use PPM resources on their own budget and well-being. However, this may not necessarily be optimal for society as a whole, as the resources may not be used efficiently. PPM has achieved remarkable success in the treat-ment of chronic conditions, their prevention and prophylaxis, in particular cancer. Pathologists occupy an unusual position on this front. As both canonical researchers and clinicians, they want to contribute to medical advancements and ensure that patients and those at risk receive optimal treatment. As representatives of clinical decision-making and therefore hospitals and specialties, ex-perts in PPM-focused pathology want to collaborate effectively to provide the necessary diagnostic tissues for oncology patients’ care. Many of these experts have serious concerns about cur-rent informed consent processes and standard tissue handling practices during clinical trials and translational studies.

Biomarkers & Targets through the View of Systems Biology, Translational applica-tions, OMICS technologies and PPM-dictated clinical approach towards decision making:

Systems biology
As the reader may sense, PPM is the grand challenge in forecasting, predicting, and pre-venting, rooted in a large and new science generated by the advances of systems biology and translational medicine. Translational biomedical research and applications will focus on “bench to bedside and back” research. In biomedical research, systems biology provides a holistic perspec-tive by assembling components at various levels - organism, tissue, or cell - rather than dissecting them individually, as seen in traditional reductionist biology approaches. This approach involves a thorough quantitative examination of how all elements within a biological system interact dy-namically over time. Interdisciplinary teams equipped with the necessary technologies and computational tools conduct this analysis in order to unravel the complex workings of biological sys-tems. In this model, biology determines what new technologies and computational methods should be developed. Once these tools are developed, they open up new avenues in biology for research. Thus, biotechnology drives technological innovation and computation, which in turn revolutionizes biology. Systems biology focuses on the systematic study of complex interactions within biologi-cal systems, utilizing highthroughput genomic technologies, such as transcriptomics, proteomics, and metabolomics. In order to achieve the challenging goal of unraveling the complexities of biological systems holistically, systems biology necessitates bridging the divide between various non-biological fields, such as information technology, mathematics, physics, and chemometrics. Systems biology employs mathematical models to analyze extensive data sets and simu-late system behavior, enabling integrative analysis of diverse types of data, thereby providing novel insights into complex biological phenomena. (Fig. 3) [3,4].

Citation:

Sergey Suchkov. Personalized and Precision Medicine (PPM) as a Unique Healthcare Model through the View of Systems Biology, Design-inspired Translational Applications and Bioinformatics-driven Support to Secure the Human Healthcare: The Role of Clinical Pathology in the Era of PPM. The Journal of Clinical Pathology 2024.