GDPbio: Genome based prediction of Diseases and Personal medicines using Bioinformatics
|G.P.S. Raghava | Department of Computational Biology | IMTECH | CRDD | Team Members | Contact | FAQ
Concept of GDPbio
Diseases and Genes
What actually they are ?
Personal drugs or personalized drugs are the drugs developed, specific to genetic constitution of an individual or sub-group of individuals. The United States Congress defines personalized medicine as "the application of genomic and molecular data to better target the delivery of health care, facilitate the discovery and clinical testing of new products, and help determine a person's predisposition to a particular disease or condition. These drugs will be more effective and showing less or no side effects. The traditional concept of one size fits to all seems to be failed while monitoring death cases due to adverse drug reactions.
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. Recent advancements in the genetic etiologies of common diseases will likely improve pharmaceutical development. Thus, "personalized medicine" is in many ways simply an extension of traditional clinical medicine taking advantage of the cutting edge of genetics research.
The field of oncology currently is feeling the greatest impact of personalized medicine. Several examples of companion diagnostic tests that now are necessary to obtain before cancer-based therapy include measuring for the erbB2 and EGFR proteins for selecting breast, lung and colorectal cancer patients for specific targeted therapies.
Examples of personalized cancer management include:
*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.
*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, Herceptin is used in the treatment of women with breast cancer in which HER2 protein is overexpressed. Tyrosine kinase inhibitors such 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 chromosome 9 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.
Recent developments in a number of molecular profiling technologies, including proteomic profiling, metabolomic analysis, and genomic/genetic testing allow the development of personalized medicine and predictive medicine, which is the combination of comprehensive molecular testing with proactive, personalized preventive medicine. It is hoped that personalized medicine will allow health care providers to focus their attention on factors specific to an individual patient to provide individualized care. The overarching concept that underpins personalized medicine is that information about a patient's protein, gene or metabolite profile could be used to tailor medical care to that individual's needs. A key attribute of personalized medicine is the development of so-called companion diagnostics, whereby specific molecular assays that measure levels of proteins or genes or specific mutations are used to stratify disease status, select from among different medications and tailor dosages, provide a specific therapy for an individual's condition, or initiate a preventative measure that is particularly suited to that patient at the time of administration. Since the aim of personalized medicine is to improve healthcare, patients will continue to benefit from advances in biomedical research and individualized treatments. Public education about the potential benefits of personalized medicine will be an important facet of its widespread acceptance.