Introduction

In our first article on Precision Medicine, we tackled the basic principles and concepts of precision medicine and diagnostics. We have discussed that precision medicine is a promising new direction in healthcare. It introduces more specificity in terms of delivering treatment to different patients by taking into account their genetic makeup, the kind of lifestyle they have, as well as the environment they are in.

We also touched upon precision diagnostics, which often serves as the first step in carrying out precision medicine approaches; it helps to identify the root of a particular disease via genetic testing, which is a type of assessment wherein a person’s genes or genome is screened for any changes that may indicate risks or cause of a particular disease. 

The first article also dealt with genomics and genetics – and the different branches they encompass – being the foundation for precision medicine, treatments developed using this approach appear more “personalized” for every individual. This is made possible by utilizing modern tools and technologies such as sequencing, omics approaches, big data, and Artificial Intelligence (AI), all of which contribute to furthering research in the field.

Finally, we have learned that through precision medicine, some drugs are made to target people with a certain gene polymorphism, diets are personalized to fit a person’s genetic makeup, cancer cells are differentiated from normal cells based on genetic profiles, diseases are detected earlier by sequencing a person’s genome, and many more. These are only some of the examples of precision medicine being used in the real world.

In this second article, we will dive deeper into the various advances and benefits of precision medicine by looking into specific applications and clinical cases of the practice. 

We will learn numerous tools and techniques as well as various applications of precision medicine such as 1) genetic testing and how it is utilized today together with conventional healthcare practices; 2) the benefits of genomic profiling and liquid biopsy and their relevance in utilizing biomarkers; and 3) how precision medicine can be applicable to multiple, different diseases such as Alzheimer’s, cancer, and cardiovascular disease. 

Thus, this second article focuses more on the real-life use and benefit of precision medicine, while also emphasizing its potential in bettering health outcomes for patients of different conditions and diseases. Read on to learn more!

Advancements in Precision Diagnostics

Precision diagnostics is an integral part of precision medicine. Apart from being utilized to diagnose complex and uncommon diseases, it is also used to identify subpopulations that respond to highly specialized (i.e., targeted) therapies, to monitor responses from treatment strategies, as well as determine drug targets, and screen for disease drivers or biomarkers related to certain disorders (Advancements in Precision Diagnostics: New Regulations and Biomarker Strategies » Precision Biospecimens, n.d.).

With the ongoing need to utilize precision medicine due to ever-changing lifestyles, and the emergence of more genetic variations and environmental hazards, more technologies are being geared towards advancing precision diagnostic tools and practices (Precision Diagnostics Technologies Innovating Healthcare Solution, n.d.).  

Here are some examples of the current advancements in precision diagnostics:

Genetic testing and its applications

This first example highlights genetic testing as well as its possible applications. 

As mentioned in the first article, genetic testing is a type of test that examines an individual’s DNA in search of genetic variations that correlate to certain diseases (Precision Diagnostics Technologies Innovating Healthcare Solution, n.d.). This tool in precision diagnostics is essential in carrying out precision medicine approaches, given that it 1) provides insight into a person’s genetic predisposition to particular diseases, 2) allows better selection of targeted therapies, and 3) determines the most optimal treatment strategies with the individual’s genetic makeup as the basis (Precision Diagnostics Technologies Innovating Healthcare Solution, n.d.). 

Some applications of genetic testing are the following:

1. Prenatal and newborn screening. In prenatal testing, the genes of the fetus are analyzed for any changes that may indicate risks of developing genetic disorders (What Are the Uses of Genetic Testing?: MedlinePlus Genetics, n.d.). Some tests may opt to look for aneuploidies, or cases wherein there is an excess or missing chromosomes (Human Genetic Testing Applications – Testing.Com, n.d.). On the other hand, newborn screening is performed after birth to screen for disorders and hopefully address them early in life (What Are the Uses of Genetic Testing?: MedlinePlus Genetics, n.d.). Some tests may include those for detecting phenylketonuria (PKU) which is a metabolic disorder, as well as sickle cell anemia, among others (Human Genetic Testing Applications – Testing.Com, n.d.).
2. Diagnostic testing. Diagnostic testing can be performed at any stage in an individual’s life but may not account for all genes or genetic conditions. Generally, this type of testing is used to verify the diagnosis of a genetic disorder based on the presenting physical symptoms (What Are the Uses of Genetic Testing?: MedlinePlus Genetics, n.d.). For these tests, experts may look at individual genes such as those for cystic fibrosis, certain types of muscular dystrophy, and sickle cell diseases (Human Genetic Testing Applications – Testing.Com, n.d.). 
3. Predictive or presymptomatic testing. These types of testing are typically used to identify gene mutations that may indicate a risk of developing a disorder that can manifest after birth or even later in life. Predictive and presymptomatic testing is also proven to be helpful for those who may not exhibit any symptoms of a particular disorder at the time of testing but have family members with known genetic disorders (What Are the Uses of Genetic Testing?: MedlinePlus Genetics, n.d.). Some diseases that these tests may target are Huntington’s disease and even some forms of cancer (Human Genetic Testing Applications – Testing.Com, n.d.).
4. Carrier testing. Carrier testing is performed to determine whether an individual possesses a copy of a genetic mutation that may develop into a genetic disorder when provided with two copies of the mutation (What Are the Uses of Genetic Testing?: MedlinePlus Genetics, n.d.). This type of testing is usually done for couples or parents who are planning for pregnancy as prenatal care. These tests may screen for genes associated with Tay-Sachs disease, and cystic fibrosis, among others (Human Genetic Testing Applications – Testing.Com, n.d.).

Genomic profiling: a tool for disease risk assessment and prevention

Genomic profiling (also often referred to as genomic testing) is a method used to provide insight into a person’s genetics by observing how their genes interact with each other as well as with their environment. Often referred to as genomic testing (depending on context), genomic profiling aims to analyze the entire genome and scan for specific genetic mutations that correspond to a disease or a prognosis of the disease such as cancer (Why Comprehensive Genomic Profiling? | Foundation Medicine, n.d.). In addition, it is through identifying changes within the genome that allows researchers to personalize treatments based on the genetic profile of the individual (Genomic Profiling | Precision Medicine – UCL – University College London, n.d.).

In precision medicine or diagnostics, genomic profiling has been key to determining biomarkers that are associated with different diseases (Genomic Profiling | Precision Medicine – UCL – University College London, n.d.). Biomarkers, in the context of precision medicine, can be proteins, genes, metabolites, and gene expression markers, among others, that can signal a particular disease or biological process that is occurring within an individual (Biomarkers and Cancer Precision Medicine, n.d.).

With regards to cancer, comprehensive genomic profiling (CGP) is a method that uses a single test to analyze a wide scope of genes that may include the genomic mutations that contribute to cancer growth (e.g., insertion-deletion or indels, base substitutions, copy number alterations, etc.) (Why Comprehensive Genomic Profiling? | Foundation Medicine, n.d.).

Illumina demonstrates this technology by utilizing a single next-generation sequencing (NGS) assay that is capable of screening for multiple, different cancer biomarkers across various tumor types in a simultaneous manner (Comprehensive Genomic Profiling (CGP) | Cancer Genomic Profiling Benefits, n.d.). These biomarkers are then used to screen for the cancer, assess its risks, and detect its presence at an earlier stage. In addition, these biomarkers are also beneficial for the accurate diagnosis and prognosis of the cancer, the prediction of the cancer’s response to treatment, surveillance, as well as monitoring response (Sarhadi & Armengol, 2022).

These aspects of genomic profiling are often the foundation of precision oncology; biomarkers aid in identifying subpopulations possessing cancer genetic mutations and the new targeted therapies are developed specifically to be effective for patients with these mutations (Sarhadi & Armengol, 2022). Therefore, genomic profiling ultimately brings biomarkers to light for the prediction, prevention, as well as risk assessment of different diseases, particularly cancer.

Liquid biopsy and its impact on cancer diagnosis and treatment

Liquid biopsy is another procedure used for cancer. Briefly, it is a non-invasive test that aims to detect portions or pieces of cancerous tumors (i.e., whole cells or molecules) in the blood or urine (Liquid Biopsy: Using Tumor DNA in Blood to Aid Cancer Care – NCI, n.d.). This contrasts with the more conventional biopsy a tissue is obtained in an area of the body suspected to have the presence of cancer. In short, a standard biopsy tells whether the cells of a tumor are cancerous, while a liquid biopsy looks for evidence of a tumor (Liquid Biopsy: What It Is & Procedure Details, n.d.).

These tumor fragments can be in the form of:

1. ctDNA or circulating tumor DNA. These are the tumor cells’ DNA fragments found in the blood which serve as their instructions.
2. CTC or circulating tumor cells. CTCs are the cancer cells that have broken off the tumor which are also found in the bloodstream. 

A blood draw for a liquid biopsy test is done to search for the cancer biomarkers (i.e., ctDNA and/or CTCs). With these biomarkers present in the bloodstream, this indicates that the patient has a cancerous tumor (Liquid Biopsy: What It Is & Procedure Details, n.d.).

While traditional biopsy is still the gold standard for diagnosing a patient with cancer (Liquid Biopsy: Using Tumor DNA in Blood to Aid Cancer Care – NCI, n.d.), information from a liquid biopsy is still valuable with regards to the development of a more targeted form of treatment.

At present, liquid biopsy can only serve as a complementing tool for traditional biopsy, with its best feature being its repeatability (as compared to tissue biopsies) (Caputo et al., 2023). As conventional biopsies are invasive and oftentimes not an option for patients whose tumors are inaccessible or have conditions that render them inapplicable for a biopsy procedure, liquid biopsies can be employed repeatedly on patients without causing much harm.

In this case, this relatively new precision oncology tool is able to monitor metastasizing cancers, especially in vital organs. In addition, liquid biopsies can track the development of cancer, assess a patient’s response to treatment, and monitor cancers in patients undergoing remission, especially those who exhibit high risks of their cancer returning (Liquid Biopsy: Using Tumor DNA in Blood to Aid Cancer Care – NCI, n.d.).

With regards to treatment, CTCs and ctDNA contain genetic information regarding the cancer which allows healthcare providers to search for the appropriate treatment that works best for the patient. As an example, some targeted therapies specifically attack cancer cells that have a certain error in their DNA, and a liquid biopsy can extract that information from the cancer cell (Liquid Biopsy: What It Is & Procedure Details, n.d.). 

Therefore, while liquid biopsy is a promising precision medicine tool for cancer, it is still in its early stages. Nevertheless, more research is currently being done to help curb the gaps in tissue biopsy. With the help of cancer biomarkers, especially ctDNAs, liquid biopsy may be utilized as a reliable diagnostic tool able to detect cancer at an earlier stage or even before the evidence of tumors.

Precision Medicine in Practice

To further illustrate the impact of precision medicine in today’s society, below are some case studies showcasing its successful applications in various areas and diseases. 

Alzheimer’s disease

In one case study involving a patient with Alzheimer’s disease (AD), researchers employed a multimodal, precision-medicine-based therapy that aims to address multifactorial dementia that is present with symptoms of AD (Ross et al., 2021).

The patient treated was a 75-year-old female with a family history of dementia and memory issues. It is also noted that the patient had mild dyslexia, and memories from her childhood and early adolescence were affected by amnesia. Apart from neurological complications, the patient also exhibited other health conditions such as Bell’s palsy, an autoimmune disorder, and increased levels of mercury, among others. There were also numerous other external contributors to her symptoms of AD brought about by her environment (e.g., exposure to molds, ticks, etc.) (Ross et al., 2021).

With the patient’s many different health issues and potential drivers of AD, the researchers aimed to target each contributor of AD with the proposed multimodal therapy.

The group took into account the patient’s individual variability by considering her total background (e.g., medical history, environment, etc.). Thus, aside from diet and exercise interventions, the researchers also evaluated and analyzed the patient’s biomarkers in order to administer tailored nutraceuticals and other medications for each of her needs. In particular, the diet introduced was personalized to reduce inflammation in her liver, which was brought about by the autoimmune disorder (Ross et al., 2021).

As for the clinical outcome, the patient has exhibited improvements in symptoms – post-treatment – over the course of 3 and a half years. Therefore, all the components involved in multimodal therapy were proven to be effective and can deliver both functional and cognitive benefits (Ross et al., 2021).

Similar to a typical precision medicine approach, the patient’s treatment took into account their individual background and medical history. With the help of the biomarkers for AD, the therapeutics administered to the patient were specialized and tailored to address their ongoing symptoms.

Cancer

Another common application of precision medicine is cancer. In 15 to 20% of all cases of invasive breast cancer in women, overexpression of human epidermal growth factor 2 or HER2 receptors is observed (Katsanis et al., 2008). HER2 receptors are essential for signal transduction pathways involved in cell proliferation and differentiation. Thus, an abundance of HER2 receptors promotes abnormal cell growth – a well-known characteristic of cancer. 

HER2 receptors are encoded by Her/neu genes. It is important to note that tumors with overexpressed Her/neu genes are known as Her2-positive, and it is only with these tumors that Herceptin, a targeted drug for early and advanced breast cancer, is prescribed (Katsanis et al., 2008). In particular, Herceptin is a monoclonal antibody and works to negate the growth and proliferation of cancer cells by binding to the HER2 receptors (Trastuzumab (Herceptin) | Cancer Information | Cancer Research UK, n.d.). This, in turn, disrupts the signaling involved in cell proliferation thereby mitigating abnormal cell division (Katsanis et al., 2008).

Numerous precision medicine studies have found that Herceptin is more effective in women with overexpressed Her2/neu genes – or those with Her2-positive tumors – than those with normal HER2 expression levels (i.e., Her2-negative). Thus, women diagnosed with early or advanced breast cancer are routinely tested for Her2/neu overexpression prior to being assessed whether they are suitable for Herceptin or other treatment options that are available (Katsanis et al., 2008).

Therefore, Her2/neu is a gene that is useful as a biomarker for breast cancer in the context of the suitability of a drug or therapeutic.

Cardiovascular disease

Another disease that greatly benefits from precision medicine and diagnostics is cardiovascular disease or CVD. 

Long QT syndrome (LQTS) is a rare, fatal form of CVD that can either be inborn or acquired. The term “long QT” refers to a characteristic wave pattern observed on the EKG that is based on the heart’s electrical signals. The QT interval is the ventricles’ electrical activity recorded on the Q and T wave patterns (as a single heartbeat is mapped into five different waves i.e., P, Q, R, S, T). Typically, a QT interval lasts only about a third of the duration of a heartbeat. However, individuals with LQST experience a longer QT interval than usual, which negatively affects the regular pacing of a heartbeat (Arrhythmias – Long QT Syndrome | NHLBI, NIH, n.d.). 

LQST arises due to malfunctioning ion channels in the heart. Ion channels allow charged atoms such as potassium, magnesium, and sodium to pass through cells in the heart, thus generating electrical signals. With LQST, the patient suffers from faulty ion channels, causing irregular electrical activity in the heart’s ventricles thereby causing life-threatening arrhythmias (Dainis & Ashley, 2018). 

Based on research, genetic testing can be used to diagnose long QT syndrome even in newborn babies. In one study, a group performed whole genome sequencing on a newborn infant which was found to present with an atrioventricular block and ventricular arrhythmias (Dainis & Ashley, 2018). 

From sequencing, the researchers were able to detect a genetic variation in KCNH2, which is a gene that encodes for potassium channels (KCNH2 Gene: MedlinePlus Genetics, n.d.) and was also recently found to be associated with LQST. Another variation was also detected in RNF207. Discovering these variants allowed the confirmation of the disease in the infant ten days after being born. In addition, this has enabled a more targeted form of pharmacotherapy to be administered, effectively addressing the affected ion channel (Dainis & Ashley, 2018).

In this case, precision medicine enabled early diagnosis of a rare condition as well as aided in delivering a more targeted and specialized form of therapy, mitigating risk, and allowing better management of the disease.

Concluding Remarks

From what has been discussed, precision medicine is and can be integrated into traditional healthcare capable of addressing multiple, different kinds of diseases. With the continuous advancement of technology, especially research in genomics, precision medicine has vast potential to improve health outcomes. 

Based on ongoing trends in research and development of precision medicine approaches, the integration of AI will be more apparent in the coming years. As more data (in the form of patient information) is collected and leveraged, algorithms can be developed to perform population stratification more effectively and accurately according to genotypes observed in patients for various diseases. 

In relation, more and more biomarkers for various conditions are also being discovered. As healthcare professionals and researchers are more enlightened on these molecular markers, improvements in accurately diagnosing and predicting the prognosis of a disease can be expected. 

Thus, it is likely that we will observe more growth in the realm of precision medicine, especially with the hopes of combating and addressing rare genetic diseases.

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