Precision medicine is a novel biomarker-guided medical practice for disease treatment and prevention. It combines knowledge of an individual’s genetic information with other social health determinants such as environment and lifestyle allowing healthcare professionals (HCP) to better understand a patient’s individual characteristics and molecular profile. This information is used to tailor personalized treatment for medical care. The unique approach offers significant benefits in improving patient outcomes, limiting disease severity, and reducing adverse effects encompassed in the provision of optimal, and timely patient-centered management.
Comprehensive genomic profiling has increased swiftly for a range of disease indications. In oncology, genomic biomarkers exist for thyroid, colorectal, bladder, breast, gastrointestinal, and lung cancer. The use of predictive biomarkers in non-small cell lung cancer (NSCLC) has been revolutionary with the testing of several biomarkers recommended by the European Society for Medical Oncology (ESMO) to support treatment decisions. For instance, a pipeline of 250+ NSCLC-related biomarkers is being investigated globally with ongoing research in several promising biomarkers including blood-based, new targetable genetic mutations, immune-related, epigenetic, proteomic, metabolomic, and microRNA biomarkers1. For all cancer types, the number of predictive biomarkers being investigated globally is considerable and steadily expanding to include pan-tumor markers such as NTRK, TMB, and MSI2.
Understanding and classifying the histologic variations of disease is transformational, but understanding its molecular profile and mechanistic associations in combination with an individual’s genetic fingerprint and allowing HCP to select the optimal regiment of the most effective treatments could be revolutionary in patient management.
As early as 1894, Professor Andrew R Robinson commented on the importance of understanding the patient, writing “it is not a question of the kind of disease (or organism) the patient has, but rather the kind of patient the disease has attacked, and an appreciation of this fact gives the best results in treatment”3. Using an individual’s genomic data to identify specific genetic mutations and/or other biomarkers associated with specific diseases, is leading to earlier and more accurate diagnosis, whereby treatment choice, regime, and dosage are optimized. Indeed, the field of pharmacogenomics which aims to use an individual’s genetic profile to predict how they may respond to different treatment drugs to achieve maximum efficacy with minimal adverse effects, avoiding unnecessary treatment and its associated social and economic costs, is evolving rapidly.
Evidence of pharmacogenetics for improved drug efficacy and safety is emerging and convincing in clinical practice. Genetic testing for mutations in the CYP2C9 and VKORC1 – two genes associated with dosing variability for the anti-coagulant Warfarin have been used clinically to optimize dosage and limit patient bleeding risk. Additionally, CYP2C9 is known to metabolize approximately 25% of clinically administered drugs including some nonsteroidal anti-inflammatory drugs where poor metabolization has led to severe clinical problems and risk of drug-related adverse events4.
Furthermore, pharmacogenetics is used clinically to personalize treatment. Specifically, in breast cancer treatment, where genetic variation in 9 genes is associated with trastuzumab resistance in people with HER2-positive breast cancer5. Similarly, the presence of genetic mutations in the epidermal growth factor receptor kinase domain has been shown to promote differential susceptibility to Erlotinib and Gefitinib in people with lung cancer 6.
Despite studies showing evidence of clinical efficacy, and recommendations from the EMA7 and FDA8 to collect DNA samples for pharmacogenetic studies during all phases of clinical development there is still a perceived lack of clinical utility. Opinions of individuals on institutional review boards and ethics committees alongside global regulations and laws currently limit the HCPs ability to collect and use DNA the DNA samples and its resulting data9. As a result, there are few suitable clinical pathways, and on a national level, genetic testing regulations are absent – more inclusive trials covering wider clinical fields are needed.
Successful implementation of pharmacogenetic testing requires sophisticated bioinformatics tools and databases capable of real-time monitoring to integrate genetic data with complex clinical information. For inclusion into routine clinical practice, the systems must be available without prohibitive cost to incorporate this information into electronic health records10.
HCP will play an essential role in the eventual adoption of pharmacogenomics into clinical practice. The genomic literacy of HCPs is critical for result interpretation and clinical decision-making to prescribe the optimal medication. In an already time-poor environment HCP commitment to genomic literacy training is critical to its broader acceptance. HCPs are the public interface, and their ability to convey the techniques will impact public engagement.
Public engagement may also be limited by concerns over the privacy and security of genetic data and its potential misuse. There is also potential for emotional distress for the individual and their family on the discovery of familial or critical disease.
Globally the breadth of funding and reimbursement systems also significantly impacts the adoption of new technologies and treatment approaches. Potential payers are reluctant to reimburse pharmacogenetic implementation and testing, and insurance plans for genetic testing are lagging even though cost analysis has shown that genome-guided interventions may be less costly when compared to standard treatment11.
It is proposed that the growing body of evidence will compel the development of public and governmental policy to promote and advance the rights of patients toward precision medicine. It is critical these policies also address ethical concerns around patient privacy and data security12. Once the policy and regulatory landscapes are defined it will likely lead to the integration of genetic testing into public and private healthcare plans. According to the International Consortium for Personalised Medicine (ICPerMed) precision medicine is logically an evolution of medicine in a biotechnology and data-rich era13.
Overall precision medicine aims to step away from the one-size fits all approach towards more accurate and suitable healthcare solutions. Integrating an individual’s genetic profile with their other health data may lead to the holy grail in medicine – the right treatment, at the right time and dose while minimizing adverse reactions. However, the question remains, do policymakers have sufficient accumulative evidence of the benefits of precision medicine to establish the political and economic frameworks to implement its standardized treatment pathways on a wider scale?
About the Author:
Anna Guildford, PhD, is a Senior Consultant with KCR Consulting.
With more than 22 years of industry experience, she is an expert in medical writing, scientific research, clinical study documentation, and an author for many academic and industry publications. She holds PhD in biomaterials and is passionate about using science to promote healthy aging and combat disease.
References
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