Precision medicine

Introduction:

Precision medicine, or ‘personalized medicine,’ is a novel, tailored approach to medical treatment that considers individual differences in patients’ genes, environments, and lifestyles. The goal is to customize medical treatment and prevention plans for each patient contrary to the ‘one-size-fits-all’ approach to achieve maximum success and minimize adverse effects of medical interventions.

Targeted Therapies

The process proceeds as follows:

• First, an individual’s DNA is analyzed to identify specific genetic mutations or variations that may influence the individual’s vulnerability to the disease, disease severity, and response to treatment.
• Then, researchers utilize specific disease biomarkers to identify particular disease characteristics at a molecular level.
• after that, based on the information gathered from genetic testing and biomarker analysis, patients are categorized into subgroups and targeted therapies against specific molecules or genes involved in the disease are developed to ensure maximum efficacy.

Pharmacogenomics

Pharmacogenomics studies how genes affect a person’s response to particular drugs. This relatively new field applies many concepts and practices involved in pharmacology and genomics to develop effective and safe medications and doses tailored to cater to any found variations in an individual’s genes. It aims to optimize drug therapy concerning the patient’s genotype to ensure maximum efficacy with minimal adverse effects. Similar to how some genes affect the color of your eyes, some genes also affect how your body uses and breaks down medicines. Differences in these genetically deduced biomechanical features can be why some people may benefit from a particular medicine while other hosts may respond to the treatment poorly. Genetic variation can also be why some severe side effects of a drug are experienced in some patients only.

• An example of pharmacogenomics application is cytochrome P450 2C19 (CYP2C19), which is an enzyme required for the metabolism of various drugs, including clopidogrel, omeprazole, pantoprazole, diazepam, phenytoin, amitriptyline, and imipramine. Some individuals have deficiencies in this enzyme, thus affecting the pharmacokinetic profile of the drugs mentioned, leading to either toxicity or diminished activity. Clopidogrel, an antiplatelet agent used in case of stable ischemic heart disease, is a prodrug that requires to be activated by CYP2C19 to perform its action; patients with deficiencies in this enzyme will not benefit from clopidogrel and will need to use alternatives. Therefore, all patients must be tested for this enzyme deficiency before receiving clopidogrel.

Uses

This approach is specifically beneficial for the treatment of various types of cancer, cardiovascular diseases, rare genetic disorders, autoimmune disorders, psychiatric disorders, diabetes mellitus, hereditary hemochromatosis, inflammatory bowel disease, neurological disorders, and AIDS.

Precision Medicine In Cancer Treatment

Since genetic mutations have a significant role in the development and progression of cancer, oncology has been leading precision medicine efforts largely. Precision medicine, by targeting specific genes responsible for the development of cancer, has the advantage of minimizing the destructive characteristic of conventional anti-neoplastic agents (ex/methotrexate), which indefinitely target all body cells, including the healthy ones, resulting in various side effects such as renal impairment, hepatitis, hair loss, and dysmenorrhea among others. For instance, (HER) -2-positive breast cancer is a type of breast cancer that tests positive for the human epidermal growth factor receptor, which promotes the growth of cancer cells and indicates a more aggressive disease course because the cancer cells grow and spread faster. About 15-20% of breast cancers are (HER)-2 positive, which were previously associated with a poorer prognosis. Still, with the development of trastuzumab, a monoclonal antibody explicitly designed against an epitope on the external domain of the HER-2 protein, treatment outcomes are dramatically improved, with a 90% survival rate. Thus, by targeting these specific genes, we spare the patient the potentially harmful effects of conventional therapy and provide them with a personalized treatment plan rendered optimal for a chance of success.

Disease Prevention

The precision medicine approach may be used in preventing diseases, as well as exterminating them. Individuals at high risk of certain illnesses are identified by searching for and detecting specific genetic variations that increase susceptibility to certain diseases. Then, genetic risk scores are used to assess the predisposition based on the genetic variants present. Gene-environment interactions can also be studied to construct preventative measures based on specific environmental factors (smoking cessation, for instance).

Limitations

• If precision medicine approaches become part of routine healthcare as anticipated, physicians and other healthcare providers will need more information regarding molecular genetics and biochemistry.
• High expenses in applying precision medicine can hinder its development. Precision medicine, in its nature, is a high-expense approach since the technology required to sequence large amounts of DNA is expensive to operate, and developing the drugs used to treat conditions based on molecular or genetic variations is likely to be costly.
• Understanding and interpreting the genetic complexity involved in treating illnesses thoroughly and indubitably is a feat that is potentially impossible to achieve.
• Precision medicine may not be equally effective for everyone due to vast genetic differences among individuals, and certain genetic variations may have unclear or contradictory implications for disease risk and treatment response.
• Other external factors such as lifestyle, socioeconomic status, diet, and environmental status all affect how diseases progress and how drugs act on the body but are usually neglected in precision medicine.

Future Research

Further research is required to optimize this approach. Examples of research areas include epigenomics and epi transcriptomics, single-cell genomics, and pharmacogenomics.

References

• König IR, Fuchs O, Hansen G, von Mutius E, Kopp MV. What is precision medicine? Eur Respir J. 2017 Oct 19;50(4):1700391. Doi: 10.1183/13993003.00391-2017. PMID: 29051268.
• MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2023 October 12]. Precision medicine; [updated 2022 May 17; reviewed 2018 Jun 01; cited 2023 December 25]; [about 5 p.]. Available from: https://medlineplus.gov/genetics/understanding/precisionmedicine/challenges/
• Thomas DC. What Does “Precision Medicine” Have to Say About Prevention? Epidemiology. 2017 Jul;28(4):479-483. doi: 10.1097/EDE.0000000000000667. PMID: 28368942; PMCID: PMC5453815.
• Desta Z, Zhao X, Shin JG, Flockhart DA. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet. 2002;41(12):913-58. doi: 10.2165/00003088-200241120-00002. PMID: 12222994.