Personalized medicine: an old or a new concept
The term personalized medicine or personalized health care has evolved as a result of the recent advances in human genome technologies that showed variations between different individuals. These advances have greatly increased our understanding of how interactions between genomic and nongenomic factors result in health and disease and in therapeutic response. They opened the door to the identification of risk factors behind many diseases and responses to therapy 1.
It is the concept of prescribing the appropriate therapeutic regimen according to with the individual’s anticipated response to a particular drug or combination of drugs, that is, to provide the right drug, at the right dosage, to the right patient, at the right time 2.
However, personalized medicine should not be thought of as a revolution. The concept of ‘treating the patient, not the disease’ dates back to Hippocrates, Garrod, Osler, and others 3.
This concept of personalized approach allows providing a ‘tailored’ health care to each individual according to his/her unique molecular and genetic profile 1. It also explains why some patients respond to targeted biological drugs, whereas others do not. Moreover, it leads to movement of the clinical trials from a ‘trial and error’ approach to a ‘knowledge-based’ treatment decision 4.
In spite of the increasing number of clinically useful molecular diagnostics and targeted therapies, there have been challenges to integrating personalized medicine into clinical practice 5.
Biomarkers: an essential contributor to personalized medicine
Another term has appeared as a result of the increasing interaction between molecular biology research and medicine and is an essential contributor to personalized medicine which is the ‘biomarker’ 6.
The widely accepted definition for the biomarker is that of the Food and Drug Administration ‘a characteristic that is objectively measured and evaluated as an indicator of normal biological and pathogenic processes, or pharmacologic responses to a therapeutic intervention’ 7.
Biomarkers include a wide variety of molecules such as proteins (proteomics), nucleic acids (genomics), metabolites (metabolomics), or even cells such as tumor cells (cytomics) 8. They may be classified according to the purpose of their use into diagnostic, prognostic, and drug–response markers 6.
Personalized medicine in dermatology
Personalized medicine and biomarkers have been used in dermatology for decades. The scope of personalized medicine in dermatology included the identification of healthy individuals at a high risk to develop a given disease (e.g. atopic dermatitis and psoriatic arthritis), stratification of patients according to groups for a more adapted therapy (e.g. urticaria, bullous diseases, malignant melanoma, and nonmelanoma skin cancers) and prognostic information (e.g. autoinflammatory skin diseases, skin cancers). It helped reducing the time, costs, and failure rate of clinical trials for new therapies 9.
Biomarkers used in dermatology
Biomarkers are well-known in dermato-oncology. The majority are used in melanoma either as a stratification marker as the V600E mutation of BRAF used to stratify the patients who are likely to respond to vemurafenib 10 or prognostic markers such as the tumor thickness, tumor-infiltrating lymphocytes, and CD2 count, which correlate closely with survival in ulcerated melanomas. Also, blood tests of the tumor marker protein S100β are used to indicate disease progression in melanoma 11. Biomarkers are used also in cutaneous squamous cell carcinoma where the active nuclear IκB kinase correlates with metastatic risk 12. KIT D816V mutation can be detected in peripheral blood leukocytes from most patients with systemic mastocytosis 13.
In dermatopharmacology, there are characteristic biomarkers available for some drugs. Azathioprine is a commonly prescribed drug in dermatology especially for autoimmune diseases such as pemphigus vulgaris. It may induce myelotoxicity in patients with low or absent thiopurine-5-methyltransferase (TPMT) activity. It is recommended to perform a TPMT enzyme activity or genetic test to avoid this side effect. Thus, TPMT is an important safety stratification biomarker 6.
Measuring glucose-6-phosphate dehydrogenase activity is another biomarker in the decision to use dapsone, which has been used for some dermatological diseases such as leprosy and dermatitis herpetiformis 6.
Measurement of HLA-DR (MHC class II) expression on blood monocytes may be another example for a safety biomarker in dermatology. Systemic administration of glucocorticoids induces a reduction in monocytic HLA-DR expression as part of its pharmacological mode of action, making it a pharmacodynamic biomarker as well. An excessive reduction, with less than 30% of positive monocytes, indicates immunoparalysis and ‘oversuppression’ associated with a serious risk to develop infection. As a result, the glucocorticoid dosage should be reduced 14.
Inflammatory skin diseases
For inflammatory skin diseases, some biomarkers have been developed. In atopic dermatitis, many biomarkers have been investigated 15–18. This includes biomarkers of lesional and nonlesional skin, blood, and urine. Urine nitrate and malondialdehyde levels were found to correlate with the severity and extent of atopic dermatitis 18. Also, serum thymus and activation-regulated chemokine are considered to be the superior serum biomarker for assessing disease severity. Additional biomarkers that could prove useful include cutaneous T-cell-attracting chemokine, sE-selectin, macrophage-derived chemokine, lactate dehydrogenase, and interleukin (IL)-18 17.
Similarly, numerous biomarkers were investigated in psoriasis. Serum 8-hydroxy-2-deoxyguanosine was suggested as a biomarker for early diagnosis, and serum human β-defensin was reported to be a useful marker for disease activity 19,20. Plasma levels of the transforming growth factor-β1, tissue inhibitors of metalloproteinases-1, matrix metalloproteinase-1, and IL-18 were found to be associated with psoriasis severity and treatment efficacy 21. Serum levels of vasoactive intestinal peptide (VIP) have been suggested as a disease severity biomarker in psoriatic patients with spondyloarthritis. VIP could also be a prognostic biomarker as patients with low-serum VIP levels appear to have worse outcomes 22. Serum human cartilage glycoprotein-39 may be used to predict cardiovascular diseases in patients with psoriasis 23. However, many of these studies were performed in small populations and additional large-scale studies are warranted to investigate these biomarker candidates. In contrast, a recent cluster analysis of gene expression profiles was performed in 150 patients with psoriasis and other inflammatory skin diseases. IL-17 tumor necrosis factor-α-associated genes specifically expressed in psoriasis were identified. Similarly, IL-36γ was suggested as a biomarker for diagnostic purposes and for the measurement of disease activity 24.
In addition, several investigations were performed to predict or correlate the response of psoriasis with individual therapies. Soluble tumor necrosis factor-α receptor type 1 in serum is discussed as a biomarker of response to phototherapy in patients 25. Recently, a correlation between treatment-associated molecular changes of genes associated with IL-23/IL-17 signaling pathways and improvement by anti-IL-23A antibody therapy was reported 26.
Personalized medicine is a promising field in dermatology where it has shown to be of great benefit.
Conflicts of interest
There are no conflicts of interest
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