Jennifer Lloyd FNP-C, MSN, OCN
PhD Student, College of Nursing
June 3rd, 2021
What is Precision Medicine?
As technology has advanced, the focus has moved from broad scoping treatments to treatments that are personalized for the individual patient. In patients with cancer, the potential of individualized treatment that is designed to target their disease has offered hope for more treatment options. In the not-too-distant future, clinician may have the ability to develop individualized treatment plans based on the genetic characteristics and identifiable targets. The clinician will be able to choose from a wide variety of treatment options to offer the best response.
Figure 1: The evolution of personalized treatment.
Note: Cancer treatments have evolved form broad topics based on signs and symptoms, treatment implementation based on evidence from clinical-trials. As technology advances, treatment algorithms will be based on individual genetic components rather than just disease state. From “Precision Medicine: Changing the way we think about healthcare”(Gameiro et al., 2018)
Cellular therapies
In 1979, the first successful transplant for leukemia of bone marrow stem cells from an unrelated donor (Rafei et al., 2019). Since that time, with the help of developments in clinical trials, genetic technology, and identification of cellular markers in cancer cells, many more cellular therapies have been developed. Engineered cellular therapies include tumor infiltrating lymphocytes (TIL), engineered T-cell receptors (TCR), cytotoxic T-cells (CTC), natural killer cells (NKC), and chimeric antigen receptor T-cell (CAR-T). Of these, only CAR-T therapies are FDA approved to treat some forms of B-cell malignancies.
The administration of CAR-T therapies has a cost in excess of ~$400,000. This limits availability of the treatment to patients with insurance that will cover the cost (Lyman et al., 2020). Other therapies are limited to clinical trials, but estimations are that the cost will be comparable to CAR-T therapies. The responses rates to CAR-T therapies clinical trials ranged from 4-25% achieving complete response (Grigor et al., 2019). Even though CAR-T is a promising therapy, there is more work to do to improve response rates.
CRISPR/Cas 9 Gene Editing
In 2020, for the first time in history two women, Dr. Emmanuella Charpentier and Dr. Jennifer Doudna, were jointly awarded the Nobel Prize in Chemistry for the discovery and development the CRISPR/Cas 9 technology. This “genetic scissor” allows scientist to insert genes of interest into target cells. https://www.nobelprize.org/prizes/chemistry/2020/press-release/
https://www.journals.elsevier.com/animal-gene/news/congratulations-charpentier-doudna-animal-gene
This technology is revolutionizing how we look at the world. Now, modifications that could take generations to breed, and be inserted directly into target cells in small labs that are accessible to many outside of large scientific research institutions. The uses also cross many disciples, not just healthcare. In produce, lettuce can be made heartier, more resistant to pathogens, with longer shelf-lives (Damerum et al., 2020).
Changing the face of cancer care
In oncology, CRISPR/Cas 9 technology has the potential to revolutionize precision medicine. It could be completely customizable to the individual patient. Cells could be targeted with for each individual patient. One of the most important aspects is that the use of this technology is much cheaper than current cellular therapies, can be upscaled more rapidly, and is highly customizable. https://www.cancer.gov/news-events/cancer-currents-blog/2020/crispr-cancer-research-treatment
Challenges
The use of CRISPR/Cas 9 technology is not without risk. The gene insertion is not 100% precise. Once initiated, the gene could be inserted into the wrong cell or at the wrong site, potentially creating other mutations. The efficacy of the treatment still needs to be determined, and if it follows the trend of other cellular therapies, response rates will initially be low. There are also many unknowns about potential side effects. First in human trials are ongoing right now. The scientific community is holding it’s collective breath at the promise gene editing to revolutionize cancer therapy.
References:
Damerum, A., Chapman, M. A., & Taylor,
G. (2020). Innovative breeding technologies in lettuce for improved
post-harvest quality. Postharvest Biology
and Technology, 168, 111266. https://doi.org/10.1016/j.postharvbio.2020.111266
Gameiro, G. R., Sinkunas, V., Liguori,
G. R., & Auler-Júnior, J. O. C. (2018). Precision Medicine: Changing the
way we think about healthcare. Clinics
(Sao Paulo, Brazil), 73,
e723-e723. https://doi.org/10.6061/clinics/2017/e723
Grigor, E. J. M., Fergusson, D., Kekre,
N., Montroy, J., Atkins, H., Seftel, M. D., Daugaard, M., Presseau, J.,
Thavorn, K., Hutton, B., Holt, R. A., & Lalu, M. M. (2019). Risks and
Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic
Review and Meta-Analysis. Transfusion
Medicine Reviews, 33(2), 98-110. https://doi.org/10.1016/j.tmrv.2019.01.005
Lyman, G. H., Nguyen, A., Snyder, S.,
Gitlin, M., & Chung, K. C. (2020). Economic Evaluation of Chimeric Antigen
Receptor T-Cell Therapy by Site of Care Among Patients With Relapsed or
Refractory Large B-Cell Lymphoma. JAMA
Network Open, 3(4), e202072. https://doi.org/10.1001/jamanetworkopen.2020.2072
Rafei,
H., Mehta, R. S., & Rezvani, K. (2019). Editorial: Cellular Therapies in
Cancer. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.02788
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