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What is Personalized Medicine?
Personalized medicine (PM) is a course of treatment catered explicitly towards an individual based on genetics, epigenetics, and clinical information. This information is used to create personalized selections of medications and therapeutic strategies tailored to an individual's specific needs. A PM approach focuses on prevention and favours proactive actions rather than reactive. Instead of having a patient undergo trial-and-error to find the best treatment course, PM narrows down potential treatments catered towards them. PM relies heavily on diagnostic tools that "allow for optimal selection of therapeutic product to improve patient outcomes" (Spandidos Publications).
Herceptin is a cancer medicine that is extremely useful in treating breast cancer. However, it is only effective in 20-30% of breast cancer patients. Those with mutations in the HER2 gene are resistant to this drug. PM would consider a patient's genetics and history to decide whether or not Herceptin would be effective. Without it, a trial-and-error approach would be required, where healthcare professionals would test and react to the outcome (improvements or no change) of a patient using Herceptin. This process can be time-consuming and cost-inefficient.
Another example is Vemurafenib (B-Raf protein inhibitor), a drug used to treat Melanoma by inhibiting mutated BRAF proteins that cause cancer. Vemurafenib only works for patients with the V600E BRAF mutation. Of all melanoma patients, 60% have the BRAF gene, and 90% of those individuals have the V600E mutation.
Who Does Personalized Medicine Involve?
Image is courtesy of Personalized Medicine Coalition.
Benefits of Personalized Medicine
Why is personalized medicine beneficial to patients, healthcare professionals, and the healthcare industry?
In 2008, a clinical trial for Crizotinib, a medication for cancer, was approached in a non-traditional sense. Usually, clinical trials progress in phases. If the medication works on the small group b in phase one, then a greater number of people are enrolled for phase two, and so on; most clinical trials fail at phase two, which results in the loss of resources and millions of dollars. The Crizotinib trial only enrolled patients who tested positive for a specific biomarker that the drug would react and target. For phase one, 82 patients were enrolled, and the results were significant; results were so significant that it only took two years to get FDA approval due to phase one's progress and success (to put into perspective, drugs usually take a decade to get FDA approval).
With this biomarker approach to clinical trials, drug development can be quicker and provide more detail into which populations benefit from the drug. The challenge, however, is that the use of biomarkers is still elusive and non-binary, as biomarkers do not provide a clear "yes" or "no" for a drug's efficiency.
Precision biomaterial devices use customized material chemistry, device fabrication, bioactive components, and/or patient data analysis to detect or treat disease or injury in a specific patient or subsets of patients. Precision biomaterials adapt to the patient with precise and specific functions.
Image is courtesy of the AAAS.
An example of this is cell separation units. Metastasis progression is variable from patient to patient and can be challenging to detect and treat. Implantable poly(lactide-co-glycolide) (PLG) scaffolds capture metastatic cancer cells. Tumor cells on the scaffold can be detected early using inverse spectroscopic optical coherence tomography, leading to a patient-specific determination of metastatic events.
Future uses include porous scaffold separator units with biomaterial sensor units that can be implanted into breast cancer patients to detect their cancer's patient-specific progression. This information can then be used to decide the most effective therapies and pathways to combat metastasis.
Challenges of Personalized Medicine
Personalized cancer therapies and pharmacogenetics can provide treatments that avoid severe toxicity (comes from patients unable to metabolize certain cytotoxic drugs) or to adjust drug doses to their condition. Genetic prognostic tests provide “information about a baseline patient or tumour characteristic that can affect the outcome (“natural history”) of the cancer, regardless of treatment.
A useful prognostic test might allow patients to be classified at low risk of relapse or death, therefore avoiding potentially toxic treatment, or at high risk and more likely to benefit from additional treatment”.
A genetic predictive test “identifies a baseline patient or tumour characteristic that suggests whether a patient is more or less likely to benefit from a specific treatment or intervention. A useful predictive test might allow therapy to be personalized for a patient based on the likelihood of benefit from the selected therapy” (MDPI).
If PM seems so beneficial, why isn’t it often used?
As a result of genetics taking a significant role in the diagnostic process with the PM approach, ethical issues arise. An example of this is pharmacogenetics. Pharmacogenetics encourages more accurate drug prescriptions to prevent serious adverse effects, providing more effective and safer drugs. However, while developing new drugs, pharmaceutical companies and pharmacogenetics will need to consider the race, gender, and genetics of patients participating in clinical trials. Not all groups of people will be tested when developing a drug, which may cause discrimination as more prominent groups are more attractive and likely to be tested over smaller groups of orphaned patients.
The utilization of race with genetic characteristics and superficial understanding of pharmacogenomics may lead to inappropriate health care...Further, this type of healthcare services is complicating and perhaps worsens inequalities and variations in healthcare delivery. Also, the pharmaceutical industry might be unconcerned with drug development which has a limited impact on a small population.
PM also requires a vast quantity of genetic information in contained in ‘biobanks.’ In regards to this, ethical issues on ownership, personal autonomy, re-identification, privacy, and sample collection arise.
Another challenge is that targeted and personalized therapies can be costly, usually ranging in the hundreds of thousands per patient.
In the Crizotinib trials, they were precise about their enrollment (using genetic tests to identify patient groups) in the first phase. They then returned to randomized controlled trials in phases two and three. An ethical issue arises when it is argued that given a patient who would have a high response rate to the drug, giving them a placebo is unethical, especially if the disease lacks effective therapies.
To summarize, the key challenges in the implementation of personalized medicine in oncology in Canada are:
Lack of consistent quality assurance and regulated laboratory oversight both nationally and provincially.
Inconsistent or nonexistent processes to assess and approve genetic tests for use and to determine what the standard of care should be.
Lack of public funding at the provincial level for specific genetic tests linked to therapeutics.
Article Author: Ashley Chen
Article Editors: Victoria Huang, Olivia Ye