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Precision Medicine: Promises Made But Not Kept?

7/6/2021

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Written by: Alexander Pralea '24
Edited by: Angelina Cho '24
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When a patient sees a medical provider, the ideal clinician strives to provide kind, compassionate care that looks beyond genetics to match the patient’s values and cultural beliefs as best as possible–so-called “personalized medicine” [1]. As medicine adopts the best features of personalized medicine–being attuned to individual preferences–it is also challenged to take advantage of data science and computational biology. This approach, called precision medicine, promises to revolutionize health delivery systems by integrating the best approaches from preventive medicine and reactive medicine, the former of which refers to actively anticipating disease and the latter of which refers to solving disease [2]. Still, logistical barriers consistently impinge on its implementation in clinical settings, raising concerns that scientists’ and clinicians’ gung-ho attitude toward it has been premature.
Precision medicine has much promise in revolutionizing the current, dated paradigm that has dominated medicine for the past hundred years. 20th-century medicine has relied considerably on the randomized-controlled trial model, which is considered the gold-standard in clinical research and a massive improvement from the intuitive medicine of old that elevated personal opinion and superstition However, it has many shortfalls, especially when diseases vary considerably from person to person in etiology (origin) and clinical presentation [3]. Such problems have plagued medical research about various disorders, such as  CFTR-RD (cystic fibrosis transmembrane conductance regulator related disorders), resulting in consistently poor prognoses. In this context, precision medicine hopes to identify particular biomarkers of disease, an approach which could be far more individualized to each patient’s unique pathophysiology.

An interesting case study for the flaws of precision medicine can be seen in pancreatic ductal adenocarcinoma (PDAC), for which molecularly targeting therapeutics has not yielded much benefit. The standard chemotherapeutic used against late-stage pancreatic cancers is gemcitabine, which while better than placebo, only improves life expectancy slightly for most patients. A 2007 study in Journal of Clinical Oncology found that combining erlotinib (a medication targeting overexpression of human epidermal growth factor receptor type I, which is often implicated in pancreatic cancers) with gemcitabine as improved life expectancy from 5.91 months to 6.24 months when compared to a treatment of gemcitabine and placebo [4]. This was one of few precision medicine studies to provide positive results for targeting PDAC, but the meager improvement in life expectancy did not justify the added emotional and financial burden of another medication. 
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Clearly, scientists and physician-scientists understand the basic science behind PDAC and other similar disorders, yet translating this into practice is difficult, mostly because targeting mutated genes with therapeutics has proven near impossible. However, painting this story as entirely negative would be flawed; while large improvements in life expectancy are still a future goal, from 2009 to 2019, five-year life expectancy has increased from 5% of PDAC patients to 8%, which immensely benefits 3% of patients, mostly due to advances in precision medicine. These researchers have determined that PDAC can be divided into various subtypes, which can be  molecularly profiled [5]. For those patients with highly actionable mutations–molecular abnormalities for which there are effective therapeutics – matched therapies have immense potential to allow patients to have higher progression-free survival (period in which the progression of disease is constant) than those whose tumors cannot be matched. It is clear that precision medicine, with its embrace of artificial intelligence and genomics, is the way ahead; yet, the complexities behind its application cannot be underestimated. We should be leery of overly ambitious claims, while still appreciating the immense advances capable of helping the most vulnerable patients.
References
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1. Article Tools [Internet]. Journal of Clinical Oncology. [cited 2021Mar21]. Available from: https://ascopubs.org/doi/10.1200/JCO.2006.07.9525?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%2B%2B0pubmed&

2. Gameiro GR, Sinkunas V, Liguori GR, Auler-Júnior JOC. Precision Medicine: Changing the way we think about healthcare [Internet]. Clinics (Sao Paulo, Brazil). Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; 2018 [cited 2021Mar21]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251254/

3. Ginsburg GS, Phillips KA. Precision Medicine: From Science To Value [Internet]. Health affairs (Project Hope). U.S. National Library of Medicine; 2018 [cited 2021Mar21]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989714/

4. Pishvaian MJ, Bender RJ, Halverson D, Rahib L, Hendifar AE, Mikhail S, et al. Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the Know Your Tumor Initiative [Internet]. Clinical Cancer Research. American Association for Cancer Research; 2018 [cited 2021Mar21]. Available from: https://clincancerres.aacrjournals.org/content/24/20/5018.long
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5. Whitcomb DC. Barriers and Research Priorities for Implementing Precision Medicine [Internet]. Pancreas. U.S. National Library of Medicine; 2019 [cited 2021Mar21]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857715/


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