الطب الشخصي Personalized medicine، هونموذج طبي يقترح تخصيص الرعاية الصحية، عن طريق قرارات وممارسات مخصصة للمريض باستخدام المعلومات الوراثية أوالمعلومات الأخرى.

الإمكانيات من المورثات إلى ما خلفها

يركز التشخيص السريري التقليدي والعلاج على العلامات السريرية والأعراض، التاريخ الطبي والعائلي، المعلومات من المعامل ونتيجة التصوير لتشخيص ومعالجة المريض. ويتبع هذا النهج غالباً بهدف العلاج، بعد ظهور أعراض وعلامات السقم.

مكن التقدم في المورثات الطبية والبشرية من فهم المزيد من تأثير المورثات على الأمراض. Large collaborative research projects (for example, the Human genome project) have laid the groundwork for the understanding of the roles of genes in normal human development and physiology, revealed single nucleotide polymorphisms (SNPs) that account for some of the genetic variability between individuals, and made possible the use of genome-wide association studies (GWAS) to examine genetic variation and risk for many common diseases.

The field of proteomics, or the comprehensive analysis and characterization of all of the proteins and protein isoforms encoded by the human genome, may eventually have a significant impact on medicine. This is because while the DNA genome is the information archive, it is the proteins that do the work of the cell: the functional aspects of the cell are controlled by and through proteins, not genes.

Important biological functions: growth, death, cellular movement and localization, differentiation, etc. are controlled by a process called signal transduction. This process is nearly entirely epi-genetic and governed by protein enzyme activity. Diseases such as cancer, while based on genomic mutations, are functionally manifest as dysfunctional protein signal transduction. Pharmaceutical interventions aim to modulate the aberrant protein activity, not genetic defect. Comparative analysis of gene expression and protein expression have largely found little concordance between the two information archives^[], thus some scientists^weasel-who? now feel a direct analysis of the proteome may be required.^[].

Historically, the pharmaceutical industry has developed medications based on empiric observations and more recently, known disease mechanisms.^[] For example, antibiotics were based on the observation that microbes produce substances that inhibit other species. Agents that lower blood pressure have typically been designed to act on certain pathways involved in hypertension (such as renal salt and water absorption, vascular contractility, and cardiac output). Medications for high cholesterol target the absorption, metabolism, and generation of cholesterol. Treatments for diabetes are aimed at improving insulin release from the pancreas and sensitivity of the muscle and fat tissues to insulin action. Thus, medications are developed based on mechanisms of disease that have been extensively studied over the past century. It is hoped that recent advancements in the genetic etiologies of common diseases will improve pharmaceutical development.

تطبيقات محتملة

Since the late 1990s, the advent of research using biobanks has brought advances in molecular biology, technologies including proteomics, metabolomic analysis, genetic testing, and molecular medicine. It is hoped^[] that information about a patient's proteomic, genetic and metabolic profile could be used to tailor medical care to that individual's needs. One idea of this medical model is the development of companion diagnostics, whereby molecular assays that measure levels of proteins, genes or specific mutations are used to provide a specific therapy for an individual's condition by stratifying disease status, selecting the proper medication and tailoring dosages to that patient's specific needs. Additionally, such methods might be used to assess a patient's risk factor for a number of conditions and tailor individual preventative treatments such as nutritional immunology^[] approaches.

In the future, tissue-derived molecular information might be combined with an individual's personal medical history, family history, and data from imaging, and other laboratory tests to develop more effective treatments for a wider variety of conditions.

Fields of Translational Research termed "-omics" (genomics, proteomics, and metabolomics) study the contribution of genes, proteins, and metabolic pathways to human physiology and variations of these pathways that can lead to disease susceptibility. These fields require in-depth knowledge in bioinformatics as well as biomedical molecular modeling and simulation. Personalized medicine research attempts to identify individual solutions based on the susceptibility profile of each individual.

Pharmacogenetics and pharmacometabolomics

Pharmacogenetics (also termed pharmacogenomics) is the field of study that examines the impact of genetic variation on the response to medications. This approach is aimed at tailoring drug therapy at a dosage that is most appropriate for an individual patient, with the potential benefits of increasing the efficacy and safety of medications. Gene-centered research may also speed the development of novel therapeutics.

It has also been demonstrated that pre-dose metabolic profiles from urine can be used to predict drug metabolism.

أمثلة على فهم الوراثة الدوائي:

• Genotyping for SNPs in genes involved in the action and metabolism of warfarin (coumadin). This medication is used clinically as an anticoagulant but requires periodic monitoring and is associated with adverse outcomes. Recently, genetic variants in the gene encoding Cytochrome P450 enzyme CYP2C9, which metabolizes warfarin, and the Vitamin K epoxide reductase gene (VKORC1), a target of coumarins, have led to commercially-available testing that enables more accurate dosing based on algorithms that take into account the age, gender, weight, and genotype of an individual.
• Genotyping variants in genes encoding Cytochrome P450 enzymes (CYP2D6, CYP2C19, and CYP2C9), which metabolize neuroleptic medications, to improve drug response and reduce side-effects.

علاج السرطان

Oncology is a field of medicine with a long history of classifying tumor stages and subtypes based on anatomic and pathologic findings. This approach includes histological examination of tumor specimens from individual patients (such as HER2/NEU in breast cancer) to look for markers associated with prognosis and likely treatment responses. Thus, "personalized medicine" was in practice long before the term was coined. New molecular testing methods have enabled an extension of this approach to include testing for global gene, protein, and protein pathway activation expression profiles and/or somatic mutations in cancer cells from patients in order to better define the prognosis in these patients and to suggest treatment options that are most likely to succeed.

Cancer genetics is a specialized field of medical genetics that is concerned with hereditary cancer risk. Currently, there are a small number of cancer predisposition syndromes in which an allele segregates in an autosomal dominant fashion, leading to significantly elevated risk for certain cancers. It is estimated that familial cancer accounts for about 5-10% of all cancers.^[] However, other genetic variants with more subtle effects on individual cancer risk may enable more precise cancer risk assessment in individuals without a strong family history.

أمثلة على علاج السرطان الشخصي:

• Testing for disease-causing mutations in the BRCA1 and BRCA2 genes, which are implicated in familial breast and ovarian cancer syndromes. Discovery of a disease-causing mutation in a family can inform "at-risk" individuals as to whether they are at higher risk for cancer and may prompt individualized prophylactic therapy including mastectomy and removal of the ovaries. This testing involves complicated personal decisions and is undertaken in the context of detailed genetic counseling. More detailed molecular stratification of breast tumors may pave the way for future tailored treatments.

• Minimal residual disease (MRD) tests are used to quantify residual cancer, enabling detection of tumor markers before physical signs and symptoms return. This assists physicians in making clinical decisions sooner than previously possible.^[]

• Targeted therapy is the use of medications designed to target aberrant molecular pathways in a subset of patients with a given cancer type. For example, trastuzumab (marketed as Herceptin) is used in the treatment of women with breast cancer in which HER2 protein is overexpressed. Tyrosine kinase inhibitors such as imatinib (marketed as Gleevec) have been developed to treat chronic myeloid leukemia (CML), in which the BCR-ABL fusion gene (the product of a reciprocal translocation between chromosomeتسعة and chromosome 22) is present in >95% of cases and produces hyperactivated abl-driven protein signaling. These medications specifically inhibit the Ableson tyrosine kinase (ABL) protein and are thus a prime example of "rational drug design" based on knowledge of disease pathophysiology.

اهتمامات

التمييز الوراثي

One of the significant barriers to genetic testing is thought to be the fear of discrimination, such as from an insurer or employer. This fear has been indicated in several polls, including the Harris Poll in 2002. For much of the 1990s and early 2000s there was legislation introduced in the United States Congress. The final resulting bill, called the Genetic Information Nondiscrimination Act, was signed by president George W. Bush in 2008. This legislation may break down a significant barrier to widespread use of genetic testing in the US. However, the measures in the law do not apply to life insurance or long-term care insurance, and the US military is also exempt.

صناعة الأدوية

The technologies underpinning personalized medicine could enable the pharmaceutical industry to develop a more efficient drug development process, based on the latest research on disease pathophysiology and genetic risk factors. Furthermore, a therapeutic agent could be marketed on the basis of a companion theranostic test result.

صناعة فهم التشخيص

The advent of molecular diagnostic tests may open new opportunities.^[]

There is little evidence that diagnostics companies are embracing partnerships with pharma companies to develop theranostics. The development risk and time to market associated with drug candidates make the development of a companion diagnostic significantly less attractive to major diagnostics manufacturers than the revenues they generate from their traditional target market of clinical laboratories. ^{dead link}

المؤمن عليهم

Personalized medicine would raise issues for those who pay for treatment. The cost of new diagnostic tests and individualized medications may be more expensive, but the predictive potential of personalized medicine could avert more costly treatments required after the onset of a disease.^[]

Insurance premiums today are based on actuarial statistics that apply to large, predictable populations. By contrast, personalized medicine targets small populations, which are far less stable and predictable from an actuarial standpoint. Payers would need to develop new actuarial assumptions on which to base their reimbursement models. Personalized medicine has the potential to reduce payers’ costs in the long term by providing the precise diagnostics required to avoid unnecessary or ineffective treatments, prevent adverse events, develop prevention strategies, and deliver more effective, targeted therapeutics. A trend towards pay for performance could accelerate the adoption of personalized medicine, if clinical data shows that targeted diagnostics and therapies reduce payers’ costs.

الأطباء

For healthcare providers, personalized medicine offers the potential to improve the quality of care, through more precise diagnostics, better therapies, and access to more accurate and up-to-date patient data. Primary care providers may have to build new service lines around prevention and wellness in order to replace revenues lost from traditional medical procedures. Physicians will require a solid background in genomics and proteomics to make the best use of the new data.

الوكالات الحكومية

The Genomics and Personalized Medicine Act was introduced in the U.S. Congress to address scientific barriers, adverse market pressures, and regulatory obstacles. In addition, U.S. Secretary of Health and Human Services Mike Leavitt created a committee known as the Secretary's Advisory Committee on Genetics Health and Society (SACGHS) to study issues related to personalized medicine.

Getting there

The key task is to find proteins, activated proteins, genes and gene variations that play a role in a disease. The first step is to associate the occurrence of a particular protein or gene variant with the incidence of a particular disease or disease predisposition - an association that can vary from one individual to another depending on many factors, including environmental circumstances. The outcome is the development of biomarkers which are stable and predictive. Today's biomarker is tomorrow's theranostic.

The infrastructure necessary includes molecular information - biological specimens derived from tissue, cells, or blood - provided on the basis of informed donor consent and suitably annotated. Clinical information is also necessary based on patient medical records or clinical trial data.

A very high level of collaboration involving scientists and specialists from varying disciplines is required to integrate and make sense of all this information. Many have given personalized medicine a shot. The most recent and promising try is by Expat Inc.

التعليم

There are several universities involved in translating the burgeoning science into use. One difficulty is that medical education in all countries does not provide adequate genetic instruction.

A small number of universities are currently developing a subspecialty in medicine that is known by several names including, molecular medicine, personalized medicine, or even prospective medicine. These include, Duke University, Harvard, The Mount Sinai Hospital in New York City. A medical school is currently being constructed in Arizona, USA to teach the field of personalized medicine; this is a project of Arizona State University and the not-for-profit Translational Genomics Research Institute (TGen). Lastly, the first private medical practice focusing solely on Personalized Medicine, Helix Health of Connecticut is currently teaching medical residents about the utility of pharmacogenomics and family history in personalized medicine.

انظر أيضاً

• Predictive medicine
• Full Genome Sequencing
• Theranostics
• تطوير الدواء
• Targeted therapy
• Translational Research
• Dynamic treatment regimes

المصادر

قراءات إضافية

• Daskalaki A, Wierling C, Herwig R (2009), Computational tools and resources for systems biology approaches in cancer.In Computational Biology - Issues and Applications in Oncology, Series: Applied Bioinformatics and Biostatistics in Cancer Research, Pham, Tuan (Ed.), Springer, New York Dordrecht Heidelberg London. 2009:227-242.
• Acharya et al. (2008), Gene Expression Signatures, clinicopathological features, and individualized therapy in breast cancer, JAMA 299: 1574.
• Sadee W, Dai Z. (2005), Pharmacogenetics/genomics and personalized medicine, Hum Mol Genet. 2005 October 15;14 Spec No. 2:R207-14.
• Steven H. Y. Wong (2006), Pharmacogenomics and Proteomics: Enabling the Practice of Personalized Medicine, American Association for Clinical Chemistry, ISBN 1-59425-046-4
• Qing Yan (2008), Pharmacogenomics in Drug Discovery and Development, Humana Press, 2008, ISBN 1-58829-887-6.
• Willard, H.W., and Ginsburg, G.S., (eds), (2009), Genomic and Personalized Medicine, Academic Press, 2009, ISBN 0-12-369420-5.
• Haile, Lisa A. (2008), Making Personalized Medicine a Reality, Genetic Engineering & Biotechnology News Vol. 28, No. 1.
• Hornberger J, Habraken H, Bloch DA. Minimum data needed on patient preferences for accurate, efficient medical decision making. Medical Care 1995; 33:297-310.
• Lyman GH, Cosler LE, Kuderer NM, Hornberger J. Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer 2007; 109(6):1011-8.
• Hornberger J, Cosler L and Lyman G. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node–negative, estrogen-receptor–positive, early-stage breast cancer. Am J Managed Care 2005; 11:313-24.
• A.Daskalaki & A.Lazakidou (2011). Quality Assurance in Healthcare Service Delivery, Nursing and Personalized Medicine: Technologies and Processes. IGI Global. ISBN 978-1-61350-120-7

وصلات خارجية

• CancerDriver : a free and open database to promote personalized medicine in oncology.