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The mystery of DNA: which drugs will save people from cancer
Artem Elmuratov, Andrey Lomonosov, Forbes, 26.05.2018
The array of human DNA data available in the world has allowed scientists to select the right treatment for a particular person and even create new drugs that hit exactly the target.
For the first time, scientists read the entire human genome 15 years ago. Since then, the cost of sequencing technology (reading the sequence of letters in the genome) has fallen exponentially, overtaking the well-known Moore's law for computers.
As a result, we now have the opportunity to use it for applied medical tasks. The new high-performance DNA decoding technology is commonly referred to as Next Generation Sequencing (NGS). The issue of the use of such technologies is especially relevant now and has become one of the topics for discussion at the St. Petersburg International Economic Forum.
To date, thousands of complete genomes have been studied and genomic data of millions of people have been obtained. Some countries conduct large-scale genotyping studies of their citizens. Many users, without getting into the appropriate program, often turn to the services of genetic laboratories themselves. As a result, an array of data obtained by scientists around the world allowed us to determine how to treat a particular person more correctly, and even create new medicines.
In this column, we will not touch on the issue of genomic editing and gene therapy, but will discuss the use of gene technologies for:
- selection of therapy taking into account genetics (pharmacogenetics);
- development and testing of drugs taking into account biomarkers;
- search for new targets and drug development based on genetic big data.
Selection of medicines taking into account the patient's DNA
The individual dosage, sensitivity and toxicity of drugs depend on the patient's genotype. At the moment, the FDA has approved more than 200 drugs that can or should be prescribed taking into account pharmacogenomic biomarkers.
This approach not only saves lives and health, but is also economically beneficial. Thus, the use of pharmacogenetic testing in the treatment of psychiatric diseases showed savings in treatment of $4,000 per patient per year.
Profitable technologies
Genetic and phenotypic data are valuable information for the development of innovative medicines "from scratch". All the world leaders developing new drugs use genomic analysis to some extent in the development of new drugs – AstraZeneca, Merck, Roche and many others.
At the moment, only a small part of medical products explicitly use or have used genomics in development – these products are grouped into the category of precision medicine. Now this market is more than $43 billion.
The next-generation sequencing market as a whole was estimated by JP Morgan at $27.7 billion in 2016. Of these, only $1.3 billion were applications in the field of agroindustry and criminology. The rest is clinical and biomedical applications.
If we talk about the prospects for the development of these areas, then by 2035 the total market volume of medical products using genome analysis will be more than $1.1 trillion (according to a study by Boston analytics for the Helsnet roadmap of the National Technology Initiative).
Drug development based on big data
The leader of the use of genetic technologies in medicine is oncology. Cancer is notorious for the problem of resistance to treatment. The possibilities of genomics for the creation of new drugs against resistant tumors have been shown by the drug osimertinib. During its development, genomic analysis of resistant tumors revealed a mutation that gives cancer cells protection and created a therapeutic antibody that indicates mutant cells to the body for their subsequent destruction. Detailed knowledge of genomics also made it possible to double the launch of this drug on the market.
What is important is that the example of the development of osimertinib shows how, thanks to the analysis of genomes and genomic diagnostics, new strategies are being born in the treatment of such complex diseases as cancer. Now the developers of new drugs can predict how the tumor will be protected, and immediately create a "model" series of drugs for consistent and successful therapy of tumors.
However, there are areas where progress in the development of pharmaceutical drugs is more difficult. First of all, these are diseases in which it is impossible to single out a single genetic target, or multifactorial diseases. These are both cardiovascular and neurodegenerative diseases. It turned out that genomics can help develop pharmaceuticals in such cases as well.
Well-known in the field of personal genomics, the American company 23andme sold part of the information accumulated over 10 years about the genotypes of customers for $ 60 million to the biotech corporation Genentech to develop a cure for Parkinson's disease. 23andme has previously entered into similar deals with other companies, including Pfizer. And now 23andme already has its own software division for the development of new products for the treatment of oncological, skin, respiratory and cardiovascular diseases.
Search for goals
Let's clarify that targets are conventionally called certain biological molecules involved in the development of the disease. Even 20 years ago, determining the target on which the molecule acts was difficult and expensive, it required a lot of tests on cell cultures, tissues and animals.
Now, with good accuracy, this can be done by computer modeling methods. In the data of the complete human genome, you can "read" information about the proteins that ensure the functioning of each cell of our body. To simulate the molecular structure of these proteins and determine which parts of the proteins perform an active function, as well as how and with what (from synthetic molecules or antibodies) this function can be blocked.
When scientists carried out this work for well-known drugs, it turned out that the genome has many times more targets for existing drugs than researchers previously thought.
The structural features of the genome are common to a significant part of those suffering from a certain disease. Analyzing the structural features of the genomes of people suffering from a certain disease and not suffering from it, it is possible to identify groups of genes and their corresponding proteins that are somehow involved in the development of this disease.
These works are called GWAS (Genome-Wide Association Studies) – studies of the association of genomic variations and diseases. They allow us to determine where the proteins involved in the development of the disease are located in the genome.
A separate interesting topic is the detailed knowledge of the genome and the functions of proteins associated with specific genes of microorganisms, which makes it possible to identify new targets – places and ways of influencing carriers of infectious diseases. In this case, we do not try to correct the mistakes of the human body, but use the vulnerabilities of pathogenic bacteria and viruses.
One of the most striking examples of recent times is the detailed decoding of the functions of the genome of the causative agent of malaria, which revealed a significant number of proteins that are functionally important for the development of this intracellular parasite – potential targets for new drugs against malaria. Previously, the creation of effective anti-malarial drugs was a big problem, since they turned out to be quite toxic or ineffective due to the resistance of the pathogen of infection.
Clinical trials of drugs taking into account biomarkers
Pharmaceutical companies are already saving huge amounts of money by using genomic data.
First, large genetic laboratories can help patients with a rare genotype in finding suitable participants in clinical trials of new drugs. The patient receives the necessary treatment, and the pharmaceutical company saves time and money on finding the right person.
Secondly, companies save a lot of money by initially targeting new drugs to a group of patients with a certain genotype.
In order to register a new drug, it is necessary to go a long way, including 3 phases of clinical trials. The development and reduction of the sequencing price made it possible to significantly optimize this path. Based on genetic studies, biomarkers are determined by which patients are selected. According to the international BIO organization, the probability of passing a drug from phase 1 to market entry increases from 8.4% to 25.9% using biomarkers. Given that the average cost of developing a new drug is usually more than $ 1 billion, the importance of using genetics for pharmaceutical is difficult to overestimate.
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