Precision medicine is a medical approach that looks at the individual variability in genes, environment, and lifestyle for each person, and uses a customized approach to tailor either a therapy or diagnostic approach to each patient/disease. It’s the opposite of the one-size-fits-all approach that is developed for many common medicines, where they’re developed for the average person and dosages are altered accordingly depending on the ailment. Instead, it’s an area that allows doctors to better predict which disease treatments will work in certain groups of people and offers a more customized and individualized therapeutic approach for patients.
Like many modern areas of advanced and specific science, the term “precision medicine” has become a bit of a buzzword, but the concepts underpinning precision medicine have been a key part of the health and medical industry for many years. Compared to mainstream therapies, precision medicine is still not as widely used, but its use is growing as more diseases start to require a more holistic approach to treatment. Here we look at some interesting pieces of research that have manifested recently in the precision medicine space.
Cancer the Main Target for Precision Medicine Research
There are many different diseases that affect humans, but cancers are one of the most widespread classes of disease with many types and many ways that they can manifest. They come with some of the harshest therapeutic treatments, and a lot of research in precision medicine involves investigating cancer, its causes, ways different cancers can be spotted, and different therapeutic options.
According to research from GlobalData, the number of non-small cell lung cancer cases is expected to rise to 1.41 million by 2029 and colorectal cancer cases are expected to rise to 1.74 million by 2031.1 These are just two examples analyzed and there are many more cancers out there that also require more efficient diagnosis mechanisms and treatments.
Open-Source Computer Platform for Cancer Clinical Trial Pairing
One example of advancement in the precision medicine space was recently published in the npj Precision Oncology journal this October (2022). Klein et al from Dana-Farber Cancer Institute have developed a computer platform, called MatchMiner, that helps clinicians to identify and match patients to appropriate therapies based on the genetic alterations of a patient’s tumor.
MatchMiner is an open-source platform—a Python-based REST application programming interface (API) server and AngularJS 1.5 client—that can be used by any oncologist to look up the potential clinical trial options for any patient by matching their trial’s eligibility criteria. The platform currently has information on over 250 clinical trials for different cancers and new trials are constantly being reviewed to see if they should be added to the growing list housed on the platform.
To demonstrate the effectiveness of pairing up patients with relevant clinical trials, the “time to consent” was evaluated on the platform. Time to consent is an analyzed metric that governs the time it takes for a patient to consent to a clinical trial after their tumor has been genetically profiled. Over the last few years of study, the platform has already identified 166 occasions where a potential match between a patient and a trial was identified, leading to the oncologist viewing the match and the patient consenting to joining the trial. It was found that those who found clinical trials through the MatchMiner platform consented 55 days earlier on average than non-platform patients, resulting in a 22% improvement.2
Pancreatic Cancer Gene Signatures for Determining Cancer Severity
Another advancement in the area of cancer diagnostics was also published in October 2022, this time looking at how mitochondrial gene signatures are linked to pancreatic cancer. Changes in metabolism are often indicators of cancer, but this research involved looking at how levels of the mitochondrial structural protein, Mic60, could be an indicator of pancreatic cancer. It’s known that dysfunctional mitochondria play a role in cancerous cell proliferation, and Mic60 is an essential protein within mitochondrial structures that influences tumor growth.
Published in PLOS ONE, Kossenkov et al found that low levels of Mic60 in a patient directly translates to aggressive disease variants, local inflammation, FOLFIRINOX failure and shortened survival rates, regardless of the age, gender, or cancer stage of the patient. It’s the first time that a gene signature of mitochondrial dysfunction has been directly linked to aggressive cancer subtypes, treatment resistance and low patient survival rates. The identification of Mic60-low gene signature in severely ill patients could become a simple point-of-service molecular tool/biomarker for estimating the cancer severity risk in pancreatic ductal adenocarcinoma (PDAC) and other cancers—such as glioblastoma.3
Targeting Amplified Genes as a Cancer Therapy
One of the recent interesting developments in cancer therapeutics came last year out of Yale University. Roger et al, publishing in Nature Biotechnology, have developed a therapeutic strategy that targets cancer-associated gene amplifications. This has been realized by activating the DNA damage response with triplex-forming oligonucleotides. These three-stranded oligonucleotides were introduced to a specific sequence on the DNA of cancer cells and it was found to drive apoptosis in the cells. On the other hand, cancers that don’t have any amplification in their DNA were found to exhibit lower levels of damage.
The research team focused on cancers that are driven by HER2 amplification, such as breast and ovarian cancer, and it was found that there are more binding sites for the triplex-forming oligonucleotides to bind to. Gene amplification is an abnormality that arises when multiple copies of a gene appear on a DNA segment, so by inserting the triplex-forming oligonucleotides at certain sequences, the duplicated genes became targets. Because of the extra targets, the damage to the DNA—through double strand breaks—was found to be significant enough that it induced apoptosis (p53-independent apoptosis), rather than the cell trying to repair itself, resulting in cancer cell death (while healthy cells remained unscathed).
The approach so far has shown an in-vivo efficacy that is in line with other precision medicine approaches. However, this way of approaching cell death could offer an alternative cancer killing route to combat drug resistance in HER-2 positive cancers.4,5
Quicker Screening for Dementia
Researchers at the University of Cambridge have found a way of detecting signs of brain impairment, up to 9 years before a dementia-related illness is diagnosed. More than 55 million people suffer with dementia worldwide and there are around 10 million new cases that manifest each year. Dementia arises from a number of neurological conditions, but it mostly commonly comes from Alzheimer’s disease; it is the seventh leading cause of death in the world and is one of the major causes of disability in older populations.6
The reason that dementia affects so many people globally is because the condition is only usually diagnosed once the symptoms start to appear, and by this point, it becomes more difficult to treat and pre-emptive measures can’t be put in place because it’s too late—the brain impairment starts many years before the symptoms arise.
Rittman et al have recently published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and have analyzed over 500,000 individuals using the UK Biobank—a biomedical database containing anonymous data on people’s genetics, health and lifestyle information. The aim of looking at all this data was to see if there were any clear pre-diagnostic signs that a person might have dementia.
To identify the pre-diagnostic signs of dementia, the scientists compared test results in problem solving, memory, reaction times and grip strength over time in both healthy patients and those that went onto develop dementia. The results showed that there are subtle cognitive impairments several years before the symptoms became so obvious that a diagnosis was sought.
It’s hoped that understanding these impairments could act as an early-warning screening tool for dementia. Biomarker testing is currently used, but the uptake of testing is currently low because these typically happen during clinical trials—by this point the patients are already on the path to dementia and the condition cannot be stopped. It’s hoped that this approach could identify potential patients before clinical trials so that the progress could be stopped and those at risk could participate in new clinical trials for dementia-related disease treatments.7
3D Printing Customized Starch Tablets
Many medicines are made with the general public in mind and are not personalized. Conventional medicines tend to be based on adult dosages, which means that children and elderly patients need to have the dosage adjusted to meet their needs. Depending on a person’s health state, their dosage may also need to be adjusted as well.
Gabilondo et al have recently published in the International Journal of Pharmaceutics and have used 3D printing methods to create easily-dissolvable tablets made of starch that offer a controlled release of drug to a patient. Different release kinetics were realized for different needs by combining different starches and geometries. 3D printing is well-known for its customized approach, and the same is true when it comes to printing medicines.
Three types of starch were used, including two types of maize starch (normal and waxy) and one type of potato starch. The research focused on hydrophobic drugs, which are often difficult drugs to formulate due to their tendency to break down and not offer a controlled release. It was found that the microporous structure of combining the starch molecules as the “tablet packing medium” was responsible for how the drug was released. By controlling this structure, some tablets were created where a drug could be released immediately for pain relief, but other tablets offered a controlled release of antibiotics over many hours, opening the door for more personalized medicine based on each person’s clinical requirements.
References
1. “Precision medicine is reshaping cancer care and will help address rising cases, says GlobalData,” GlobalData (2022). https://www.globaldata.com/media/medical-devices/precision-medicine-reshaping-cancer-care-will-help-address-rising-cases-says-globaldata/
2. Klein, H., Mazor, T., Siegel, E. et al. MatchMiner: an open-source platform for cancer precision medicine. npj Precis. Onc. 6, 69 (2022). https://doi.org/10.1038/s41698-022-00312-5
3. Kossenkov AV, Milcarek A, Notta F, Jang G-H, Wilson JM, Gallinger S, et al. (2022) Mitochondrial fitness and cancer risk. PLoS ONE 17(10): e0273520. https://doi.org/10.1371/journal.pone.0273520
4. “Building the Next Platform for Precision Medicine,” Article by Emily Montemerlo, Yale School of Medicine (2022). https://medicine.yale.edu/news-article/building-the-next-platform-for-precision-medicine/
5. Kaushik Tiwari, M., Colon-Rios, D.A., Tumu, H.C.R. et al. Direct targeting of amplified gene loci for proapoptotic anticancer therapy. Nat Biotechnol 40, 325–334 (2022). https://doi.org/10.1038/s41587-021-01057-5
6. “Dementia,” Fact Sheet, World Health Organization (2022). https://www.who.int/news-room/fact-sheets/detail/dementia
7. Swaddiwudhipong, N, Whiteside, DJ, Hezemans, FH, Street, D, Rowe, JB, Rittman, T. Pre-diagnostic cognitive and functional impairment in multiple sporadic neurodegenerative diseases. Alzheimer's Dement. 2022; 1- 12. https://doi.org/10.1002/alz.12802
8. Kizkitza González, Izaskun Larraza, Garazi Berra, Arantxa Eceiza, Nagore Gabilondo, 3D printing of customized all-starch tablets with combined release kinetics, International Journal of Pharmaceutics, Volume 622, 2022, 121872, https://doi.org/10.1016/j.ijpharm.2022.121872
9. “3D printing of starch for personalised medicine development,” Campusa, The University of Basque Country magazine (2022). https://www.ehu.eus/en/web/campusa-magazine/-/3d-printing-of-starch-for-personalised-medicine-development