When someone goes to the doctor, the attending physician treats (after history taking and physical examination plus some laboratory tests) the patient according to his/her illness, taking into consideration the patient's background data. This is personalised medicine (PM).
However, the current definition of PM has evolved, taking advantage of the great advances made in molecular sciences and the unraveling of the human genome (fully sequenced in 2003), plus the understanding of how diseases take root and progress in our bodies.
Aside from genes, what are just as important are the proteins that carry out cellular functions such as cell growth, cell death, differentiation, etc. The process whereby these biological functions are controlled is called signal transduction. This process is entirely epi-genetic (epigenetics, literally "on" genes, refers to all modifications to genes other than changes in the DNA sequence itself), and governed by protein enzyme activity.
The key task is to identify 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.
Hence, PM is about making the treatment as individualised as the disease. It involves identifying genetic, genomic, and clinical information that allows accurate predictions to be made about a person's susceptibility of developing disease, the course of disease, and its response to treatment.
Unlike traditional approaches whereby treatment is in response to the appearance of symptoms and signs, ie after the disease has appeared, PM seeks to modify the disease even before it appears.
Physicians often talk about "personalised medicine": the idea that therapies should be tailored to each patient's unique genetic and medical profile.
What are the potential benefits?
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 in order to better define the prognosis in these patients and to suggest treatment options that are most likely to succeed.
For example, take the testing for disease-causing mutations in the BRCA1 and BRCA2 genes, which are implicated in familial breast and ovarian cancer syndromes. The discovery of this disease-causing mutation can inform "at-risk" individuals as to whether they are at higher risk, and may prompt individualised prophylactic therapy, including mastectomy and removal of the ovaries. This testing involves complicated personal decisions, and is undertaken in the context of detailed genetic counselling.
Targeted therapy is the use of medications designed to target aberrant or abnormal molecular pathways in a subset of patients with a given cancer type. An example is trastuzumab, which is used in the treatment of women with breast cancer in which HER2 protein is overexpressed.
Granted, most cancers cannot be stopped at a single signal transduction inhibition, but it has given impetus to model drugs on mutant proteins, and this has shortened the development of new anti-cancer drugs. Hence, PM potentially allows more targeted and effective drugs to be developed, resulting in better treatment results.
Minimal residual disease (MRD) tests are used to quantify residual cancer, enabling detection of tumour markers before physical signs and symptoms return. This assists physicians in making clinical decisions sooner than previously possible. The ability to pick up early cancer in susceptible patients will result in better treatment results, and perhaps allow for more savings in cost.
PM 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.
The technologies underpinning PM 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.
The development of drugs based on abnormal gene expression is a rational approach and results in faster development of drugs. This is a far more efficient method to discover new drugs, as compared to the old approach of randomly checking through thousands of chemical compounds.
How PM affects patients
How PM affects patients
For healthcare providers, PM offers the potential to improve quality of care through more precise diagnostics, better therapies, and access to more accurate and up-to-date patient data. Physicians will require a solid background in genomics and proteomics to make the best use of the new data.
Recently, a scientist at Stanford University, United States, decided to subject himself to state-of-the-art genome sequencing, followed by regular monitoring and other chemical tests thought to reflect his health status.
This genome study will show what illnesses he is susceptible to, while the other tests will reflect the real time changes in his body.
In all, the team crunched three billion measurements gathered over 20 time points, tracking close to 40,000 variables. The typical blood panel a patient gets for routine medical visits looks at about 20 variables. For all that hard work, he was discovered to have versions of genes that put him at risk of type 2 diabetes. He was diagnosed to have diabetes, and the early detection may have impacted his disease outlook.
Obviously, the same approach cannot be repeated for the general public. The sheer cost and man-hours in repeatedly performing the wide array of tests would be a formidable challenge.
In the future, gene sequencing will be faster and cheaper, making tests far more affordable, while the monitoring tests will be fine-tuned to a far smaller number of tests, which are clinically relevant. Hence, it is likely to become a doable undertaking in the future.
Not only for the sick
Because an individual's genome influences his or her likelihood of developing (or not developing) a broad range of medical conditions, personalised medicine focuses strongly on wellness and disease prevention.
For example, if a person's genomic information indicates a higher-than-average risk of developing diabetes or a particular form of cancer, that person may choose a lifestyle, or sometimes be prescribed medications, to better regulate the aspects of health and wellness over which he or she has control.
The person may benefit in the long run from making preventive lifestyle choices like diet control, weight control and regular exercise, that will help counteract the biological risk.
Genomic medicine may help determine a person's risk of developing several specific medical conditions, including cancer, cardiovascular disease, obesity, neurodegenerative diseases and neuropsychiatric disorders. Researchers are actively investigating the genomic and genetic mechanisms behind these, and developing predictive testing for such diverse medical conditions.
The day of routine genome studies and sequencing has not yet arrived, but the cost has come down significantly over the past few years. How we utilise the tremendous amount of information gathered from gene sequencing studies, and put it to productive use remains a challenge.
In a recent study, researchers found that most people would get negative results from having their genome sequenced for all but one of 24 identified conditions that includes heart disease, diabetes and Alzheimer's. While the process can help spot many rare genetic disorders, it doesn't appear to be a good predictor of who will suffer from the majority of illnesses.
Eric Topol, director of Scripps Translational Science Institute in La Jolla, California, said the results show sequencing is still at a very early stage. "This is a moving target, a dynamic field, and we may have a better idea on how to utilise the data after a large number of patients (up to millions) have been sequenced."
Physicians all dream of giving the right treatment at right dose to the right patient, at the right time, with the right outcome. PM may just make our dream come true - hopefully in the not-too-distant future.