• November 16, 2022
• By admin

Precision Medicine Will Force Out the One-Size-Fits-All Approach

What exactly is Personalized Medicine?

What would you do if someone you care about was diagnosed with a serious illness? Imagine that the medicine and dosage they receive to cure their disease are precisely tailored to their symptoms, resulting in minimal side effects and a high chance of survival/cure.

Predicting this precise and individual response to therapy is the goal of personalised medicine. To elaborate, it is the tailoring of medical treatment to a patient’s individual characteristics, symptoms, and responses at all stages of care. Prevention, diagnosis via next-generation sequencing (NGS), biomarkers, treatment, and follow-up Precision medicine, stratified medicine, targeted medicine, and pharmacogenomics are all terms that are frequently used interchangeably with personalised medicine. The National Academy of Sciences (NAS) defines precision medicine as “the use of genomic, epigenomic, exposure, and other data to define individual patterns of disease, potentially leading to better individual treatment.” ‘Stratification’ is a subset of personalised medicine that refers to the classification of patients based on disease symptoms, drug responses, and disease.

A personalised approach to medicine, according to the National Human Genome Research Institute, includes using a “individual’s genetic profile to guide decisions about disease prevention, diagnosis, and treatment.”

More than 20 years ago, the ambitious plan to sequence the first reference human genome gave birth to personalised medicine. This was accomplished in 2003 at the Sanger Centre in Cambridge, when they had an essentially complete sequence and map of all the genes in the human body for the first time.

Personalized medicine advancements have already resulted in powerful new discoveries and several new FDA-approved treatments that are tailored to an individual’s genetic makeup or the genetic profile of a patient’s tumour. It is now common practise for cancer patients to undergo molecular testing via NGS as part of their treatment. The identification of specific biomarkers through diagnostic testing enables physicians to choose treatments that increase the likelihood of survival while minimising the risk of adverse effects.

Personalized medicine extends beyond pharmaceutical and immunotherapy interventions. Imaging, sensor, interoperable device, and mobile/wireless capabilities have enabled treatments that take a patient’s genetic, anatomical, and physiological make-up into account.

What makes Personalized Medicine unique?

Currently, healthcare is characterised by a reactive “one-size-fits-all” approach to patient care. As with personal training or even personal shopping preferences, there is now a shift toward a system of predictive, preventive, and precision care based on an individual patient’s needs in personalised medicine. Personalized medicine focuses on the discovery of biomarkers and genetic signatures for disease prevention and therapeutic response prediction. It also aids in raising a patient’s awareness of individual lifestyle changes that may aid in preventing the disease from returning or even occurring in the first place.

Oncology, cardiovascular diseases, neurodegenerative diseases, psychiatric disorders, diabetes and obesity, arthritis, pain, and Alzheimer’s disease are currently areas where personalised approaches are particularly promising. This personalised molecular medicine approach has the potential to improve health outcomes, treatments, and reduce toxicity due to adverse drug reactions.

Current treatment practises revolve around “standards of care,” or the best prevention or treatment options for the general population, or the average person on the street. In the case of breast cancer, those standards imply mammograms after a certain age and the usual chemotherapy to treat a tumour if one is discovered. Instead of determining which defective gene caused the disease through biomarker identification, doctors simply move on.

In 2007, a forward-thinking research project involving volunteers, physicians, scientists, ethicists, genetic counsellors, pharmacists, information technologists, and hospital and academic partners was launched to investigate the use of genomic information in clinical decision-making.

Next-Generation Sequencing (NGS)

The application of Next Generation Sequencing (NGS) is critical to unlocking the potential of personalised medicine. The cost of sequencing a human genome has dropped dramatically thanks to NGS, from $100 million in 2002 to $1,000 today. NGS, which stands for next generation sequencing, refers to the DNA sequencing methods that followed capillary-based Sanger sequencing (first generation) in 2005. Unfortunately, the widespread adoption of NGS-led personalised medicine in hospitals is still hampered by financial constraints. The availability of low-cost automated systems for sequencing DNA or spot-checking for genetic variation is critical to progress in both research and clinical applications, and this is driving the demand for new tools adapted to Next Generation Sequencing equipment.

Illumina (TruSeq, HiSeq), Life Technologies (Ion Torrent, SOLiD), Complete Genomics (DNA nanoball sequencing), 454 Sequencing (pyrosequencing), and Oxford Nanopore Technologies are among the current next generation DNA and RNA sequencing companies (GridION).

The need for faster, cheaper, and more accurate sequencing technologies is driving down costs and improving technology, pushing the research community and academic medical centres to transform how cancer is diagnosed and treated.

Disease biomarkers’ role in personalised medicine

As previously stated, phenotypically similar conditions classified as the same disease can result from a variety of genetic polymorphisms or mutations. Similarly, diseases that affect specific organs, such as cancer and systemic inflammatory diseases, may be triggered by a single shared molecular mechanism. Biochemical, genetic, genomic, and other markers that indicate such mechanisms can be used to identify specific disease mechanisms and diseases. These specific biomarkers can be developed into diagnostics that identify a specific mechanism involved in a patient’s disease. The study of these biological mechanisms will allow diseases to be classified based on their underlying mechanisms and pathways rather than pathophysiology, pathology, and phenomenology alone.

Patients must be chosen based on the presence or absence of specific diagnostic biomarkers in order to develop individually targeted medicines. In some cases, that may be a small subset of the patient population defined solely by disease.

Traditionally, a drug would be tested on a population of breast cancer patients. Patients can be chosen based on a similar disease pathway, i.e. being Her-2 positive, using NGS and biomarker analysis. Because the tumours are caused by the same molecular mechanisms, using biomarkers in this manner allows for the treatment of patients with malignant tumours in other organs with the same medicine. In terms of clinical trials, this method of medical intervention results in smaller and, hopefully, more homogeneous groups.

What Personalized Medicine therapies are available?

Since the completion of the Human Genome Project, researchers have discovered over 1,800 disease genes. There are now over 2,000 genetic tests for human conditions available, with 350 biotechnology-based products in clinical trials.

Treating the underlying absent protein rather than the symptoms caused by the protein’s absence has resulted in faster drug approval via ‘priority review’ and a well-prepared drug submission with strong evidence that the treatment offers significant advancements in treatment.

Kalydeco is one of several “targeted therapies” approved for Cystic Fibrosis in recent years (CF). KalydecoTM (ivacaftor) was approved for patients with a specific genetic mutation known as the G551D mutation in a gene that is important for regulating the transport of salt and water in the body. There are hundreds of known mutations that can cause CF; however, the G551D mutation accounts for only 4% of cases in the United States (approximately 1200 people). Kalydeco allows a proper flow of salt and water on the surface of the lungs in patients with this mutation, preventing the accumulation of sticky mucus that occurs in CF patients and frequently leads to life-threatening lung infections.

In terms of personalised medicine, lung cancer treatment is one of the most advanced areas. alectinib (Alecensa, Genentech, Inc., (NYSE: DNA)), gefitinib (Iressa, AstraZeneca Pharmaceuticals, PLC (NYSE: AZN)), necitumumab (Portrazza, Eli Lilly and Co (NYSE: LLY)), nivolumab (Opdivo, Bristol-Myers Squibb Co (NYSE: BMY)), osi Most cancer immunotherapies are designed to be ‘targeted’ to specific antigens on cancer cells, thereby destroying only cancer cells while sparing healthy ‘normal’ cells. The administered Monoclonal Antibody (mAb) or the antibody produced by the body in response to a vaccine interacts with the targeted antigen, triggering a chain of events that results in tumour cell death.

How can we use personalised medicine to treat more diseases?

An unprecedented collaboration has recently been reported between GlaxoSmithKline PLC (NYSE: GSK), Amgen Inc (NASDAQ: AMGN), and Celgene Corp (NASDAQ: CELG) and biotech companies such as NantWorks, NantKwest, and Precision Biologics.

These pharmaceutical behemoths will collaborate with community oncologists and some of the country’s most prestigious academic institutions to accelerate the potential of combination immunotherapies. This collaboration will provide researchers with access to more than 60 experimental and approved immunotherapy medicines, allowing them to test different combinations on up to 20 tumour types in as many as 20,000 patients by 2020. It is hoped that this collaboration between these major cancer therapeutic players will aid in the advancement of cancer treatment.

Representatives from 15 countries’ governments, healthcare providers, academia, and industry recently met in the United Kingdom to discuss collaborations aimed at developing their local genomics capability. One of the topics discussed during the two-day conference was systematic, long-term planning for the integration of genomic and personalised medicine into the day-to-day delivery of health care in the United Kingdom.

‘The impact of the genomics revolution on global health – how can governments respond?’ was the title of the event. Unfortunately, the patients themselves, as well as the insurance companies or health organisations that must pay for the treatments, are the limiting factors to the advancement of personalised medicine. This is well described by Edward Abrahams, president of the Personalized Medicine Coalition in Washington, D.C. “You want to see evidence before you’re charged.”

What will the future bring?

Oncology has traditionally been at the forefront of personalised medicine. However, breakthroughs in other areas, such as infectious diseases and hemostasis, have occurred in recent decades. A number of biomarker candidates have recently been identified that link mode of action to disease pathophysiology in chronic inflammatory conditions such as rheumatoid arthritis and asthma.

There has also been significant progress in stem cell and regenerative medicine, which offer the possibility of replacing or regenerating missing or damaged tissues.

As previously stated, ongoing collaboration is required to ensure the accuracy of genetic tests for the detection of genetic variants. PrecisionFDA is a growing FDA-driven informatics community in the United States with a supporting platform. PrecisionFDA will provide a platform for the community to test, pilot, and validate new approaches. NGS test developers, researchers, and other members of the community, for example, can use precisionFDA to share and cross-validate their tests or results against crowd-sourced reference material.

Only in March of this year, a team of scientists led by Dr Sergio Quezada and Professor Charles Swanton made a ground-breaking discovery in understanding how the genetic complexity of cancerous tumours can be recognised and exploited by the immune system, even when the disease is in its advanced stages.

Professor Charles Swanton described the study as follows: “This paves the way for researchers to examine individual patients’ tumours and profile all antigen variations to determine the best ways for immunotherapy treatments to work, prioritising antigens found in every tumour cell and identifying immune T-cells that recognise them. This is fascinating, and it pushes personalised medicine to its logical conclusion, with each patient receiving a unique, bespoke treatment.”

While some patients may be experiencing the benefits of personalised medicine in some areas, others are far behind. Consider patients suffering from depression, 38% of whom do not respond to the first medication prescribed to them. Or patients with asthma, 40% of whom do not respond to the most commonly used medications.