Personalized health and medicine

What do we mean by personalized and precision medicine?

Personalized health and medicine. Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability, including genetic factors, environment, and lifestyle. This approach will allow physicians and researchers to more accurately predict which treatment and prevention strategies for a given disease will be effective in specific groups of people.

The terms “precision medicine” and “personalized medicine” are often used interchangeably, but they don't mean exactly the same thing. “Personalized medicine” is an older term that has been replaced by “precision medicine” to avoid the misinterpretation that treatments and preventative measures are developed exclusively for each individual.

In precision medicine, the focus is on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors (1).

This new perspective represents a fundamental shift away from the "one-size-fits-all" paradigm for clinical treatment, evolving towards innovative approaches, such as patient-tailored therapies, with the aim of achieving better outcomes (2). Therefore, in the coming years, medicine will gradually move from being reactive and disease-based to being health-centered. This type of medicine is commonly referred to as P5 Medicine, as it is personalized, predictive, preventive, participatory, and population-based.

This new way of understanding medicine is personalized, because it is based on each person's genetic, environmental, and lifestyle information; predictive, because this personalized information allows us to determine the individual risk of suffering from certain diseases; preventive, because, based on the prediction of that risk, prophylactic measures (both lifestyle and therapeutic) can be established to reduce it; participatory, because many prophylactic interventions require patient participation and a change in the doctor-patient relationship; and population, because it offers the possibility of making the system more efficient and thus, with the same resources, being able to serve a larger population (3).

In general, we can divide precision medicine into three main branches: prevention, diagnosis, and treatment.

• Regarding prevention, We can say that advances in patient screening, based on family history and the identification of genetic variants associated with a higher probability of disease occurrence, have led to remarkable improvements in prevention for specific at-risk populations (4).
• Regarding the diagnosis, Precision medicine involves new, more complex diagnostic classifications based on genetic factors, biomarkers, and phenotypic or psychosocial factors, which differentiate subgroups of patients within a specific disease. A biomarker, or biological marker, is defined as a characteristic that can be objectively measured and evaluated as an indicator of a normal biological process, a pathological process, or a pharmacological response to a therapeutic intervention (5).
• On the other hand, precision medicine includes the development of new treatments Personalized treatments applicable only to specific groups of patients who suffer from the same disease; this is what is known as pharmacogenetics.

Pharmacogenetics

Pharmacogenetics is a branch of precision medicine that studies how a person's genetic makeup influences their response to medications. The Food and Drug Administration (FDA) currently includes pharmacogenetic information on the labels of about 200 medications. This information consists of measurable or identifiable genetic information that can be used to individualize medication use (6,7).

The era of “omics” and its importance in precision medicine.

The dissemination of “multi-omics” analyses, along with access to large-scale clinical, behavioral, and environmental information, will allow the digitization of each person's health status or disease, and create a global health management system capable of generating real-time knowledge and new opportunities for prevention and therapy. (9)

Omics sciences can be defined as the part of biology that analyzes the structure and functions of a given biological system at different levels, including:

• Genomics: identification of genetic variants associated with the disease, the response to treatment, or the future prognosis of patients.
• Epigenomics: characterization of reversible modifications of DNA or DNA-associated proteins.
• Transcriptomics: study of the RNA resulting from the expression of a cell.
• Proteomics: large-scale study of proteins.
• Metabolomics: study of multiple types of small molecules, such as amino acids, fatty acids, carbohydrates, or other products of cellular metabolic functions.
• Metagenomics: study of a mixture of genetic material extracted from a community of organisms.

Genomics is the most developed of the omics sciences, although the other fields are very promising. Within the field of medical research, genomics focuses on identifying genetic variants associated with disease, treatment response, or the patient's future prognosis.

Genome-wide association studies (GWAS) are widely used in this field. This successful approach has been used to identify thousands of genetic variants associated with complex diseases in multiple human populations. In these studies, millions of genetic markers are analyzed in thousands of people, and the differences between cases and controls are considered evidence of association. GWAS studies make an invaluable contribution to our understanding of complex phenotypes (10,11).

In the future, combining knowledge from different omics sciences will be essential, allowing for a comprehensive and detailed view of individuals from a molecular perspective, thus enabling precision medicine. Omics sciences will be key in early diagnosis, in selecting the best treatment, and in developing new preventive intervention technologies.

Examples of applications of precision medicine

Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia.

Population-attributable risk models estimate that up to one-third of AD cases can be prevented by modifying risk factors. The field of AD prevention has largely focused on addressing these factors through universal risk-reduction strategies for the general population. However, targeting these strategies toward clinical precision medicine, including the use of genetic risk factors, allows for a potentially greater impact on reducing AD risk (12).

On the other hand, it is known that neuroinflammation begins decades before the clinical onset of Alzheimer's disease and represents one of the first alterations in the entire disease process. Large-scale genome-wide association studies (GWAS) point to several genetic variants—including TREML2, CD33, CR1, MS4A, CLU, and EPHA1—potentially linked to neuroinflammation. Most of these genes are involved in proinflammatory intracellular signaling, cytokines/interleukins/cell turnover, synaptic activity, lipid metabolism, and vesicle trafficking (13).

PD-L1 in cancer

Cancer is a term that describes diseases in which abnormal cells multiply uncontrollably and invade nearby tissues. Rather than a single disease, it is a group of more than 200 diseases that share a number of characteristics leading to uncontrolled cell growth. Therefore, it exhibits great heterogeneity, making it essential to select a specific treatment regimen for each patient. This treatment selection involves evaluating the patient's overall risk in the absence of treatment, the patient's benefit from treatment, and the potential adverse effects of treatment (14).

A specific example of a biomarker used for this purpose is the PD-L1 protein, whose biological function is to prevent immune system cells from attacking healthy cells. When a cell expresses PD-L1, it signals to the immune system that it is a healthy cell and should not be attacked. However, sometimes tumor cells can also express PD-L1, causing the immune system to fail to recognize them as tumor cells and instead fight the tumor.

Numerous therapeutic options exist based on “anti-PD-L1,” which neutralize PD-L1 expression and make the tumor vulnerable to the body's own immune cells. Therefore, the tumor's expression of PD-L1 allows us to determine the response to treatment (15).

Warfarin (pharmacogenetics)

Warfarin is an oral anticoagulant used worldwide to treat and prevent thrombotic disorders. Although highly effective, it has a very narrow therapeutic index, making accurate dosing difficult.

Genetic variants of the cytochrome P450-2C9 and vitamin K epoxide reductase complex enzymes, encoded by the CYP2C9 and VKORC1 genes, respectively, along with non-genetic factors, affect warfarin dosage variability. Patients with specific variants in one of these two genes may require a lower dose of warfarin compared to patients without these variants.

Furthermore, the combination of genetic variants in both genes (CYP2C9 and VKORC1), along with clinical factors, can put some patients at risk of adverse events such as bleeding. Therefore, it is essential to know the patient's genotype for these variants in order to avoid this and other potential adverse effects (16, 17).

Zogen's Health Check Test and Pharmacogenetics: A First Step Towards Personalized Medicine

At Zogen we offer preventative tests for salud called Health Check y Pharmacogenetics, These tools offer a wealth of scientifically validated information, telling you which aspects of your health and well-being require the most attention. It provides a comprehensive overview of your health, making it a valuable preventative tool and a crucial first step towards personalized medicine.  

Literature

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