Cancer treatment methods
6 Facts about Cell Mutation, Targeted Drugs
and approaches to the treatment of oncological diseases
Peter Fedichev, Post-scienceCancer has been known to mankind for a long time.
This is a disease in the treatment of which, throughout the history of mankind, almost no success has been achieved. With the advent of antibiotics, people have almost forgotten about terrible infections, ranging from plague to syphilis. However, as the world's population ages, the probability for each of us to encounter cancer in life is constantly growing. Unfortunately, despite the hundreds of billions of dollars that have been spent in developed countries since the late 80s, and decades of research, we do not see a significant breakthrough in cancer treatment.
The increase in the life expectancy of cancer patients over the past 20-30 years was not due to the fact that revolutionary therapies appeared, but mainly because cancer began to be diagnosed at an earlier stage. The problem is that medicine allows you to diagnose the disease at the stage when, without treatment, literally in a year, the number of cells in a cancerous tumor will be such that the weight or volume of the tumor will be measured in hundreds of grams.
1. Genetic backgroundThe human body, like the body of any animal, contains in its genome genes that are used by cancer for its development.
At first glance, it seems illogical. In order to grow out of one cell and turn into a human being, it is necessary to use mechanisms that are dangerous or unnecessary in adulthood. In particular, in order to prevent the rejection of the fetus from the mother, the cells of the embryo learn to deceive her immune system, posing as "their own", and thus prevent the mother's immune system from destroying the embryo. There are a lot of pathologies associated with this. This is a profitable acquisition of evolution, but these same genes, when activated in adulthood, can help a cancer cell to deceive the immune system and prevent the destruction of cancer cells.
2. Age-related causes of cancerIn fact, there are millions of cancer cells in the body of every healthy adult, which are in balance with the body, are constantly detected and destroyed by cells of the immune system.
However, with age, the number of possible errors in the execution of the genetic program begins to increase, and at some point the amount of stress exceeds the capabilities of damage control systems. At this point, the cancer cells are released. The danger lies in the fact that by all signs these are cells of the same organism. At first, they have almost the same genetic code as all other human cells, and this does not allow defense systems to quickly identify them.
3. Mutation of cancer cellsCancer cells begin to mutate rapidly, and new copies of this genome fight against the body's defense systems.
New forms of these cells arise, which are absolutely unlike either the original cells or the cells of any other patient. Studies show that in the cancerous tumor of the same patient there is not one type of cancer, but many types. In fact, we are not talking about fighting any one disease, but fighting different, rather dissimilar forms of the disease. In this sense, there is no one disease – cancer. There are a huge number of different forms of cancer, and even in the case of each patient, a lot of different forms of cancer are realized simultaneously. It is for this reason that an effective means of controlling a cancerous tumor, except for surgery and very aggressive forms of chemo or radiotherapy, has not been invented.
4. Lack of anti-cancer therapiesAnother complicating circumstance is that it is the immunity that is the main protection of a person from a cancerous tumor.
Immune system cells and tumor cells divide rapidly, and most therapies aimed at destroying rapidly dividing cells simultaneously lead to the destruction or suppression of immune functions. Thus, many therapies lead to the fact that the body receives severe toxicological damage and at the same time the immune system is suppressed. We are talking about the fact that for a lot of money in very expensive hospitals, the patient's life time increases by less than a year.
5. The possibilities of targeted drugsIn this regard, the question arises: where to get a reason to hope that cancer will ever be cured?
Rapid progress cannot be expected, but recent studies give some hope. We need to look for ways to distinguish between cancer and healthy cells and come up with targeted, specific therapies that allow the immune system to either recognize or specifically destroy those cells that are very different from healthy tissue cells.
Significant progress has been made on this path in recent years. In particular, targeted drugs have been developed for some types of cancer that allow them to act against very specific genes activated only in cancer cells. Thus, in recent years, significant progress has been achieved in pediatric oncology, where the percentage of surviving patients has been significantly increased. It was also possible to get a great response ("patient response") in some forms of cancer, for example breast cancer. Specific markers were developed that made it possible to identify the population of patients for whom certain specific drugs would be useful, and to obtain a very large percentage of cure in specific categories, even for small groups of patients.
This approach has certain advantages, but it also has disadvantages. In order to apply a pill or therapy, you will first have to genotype people, and then determine that, for example, only 2% of 100% of people will be able to get a response to this therapy. This makes clinical research in oncology extremely difficult. If only a percentage or a few percent of the entire patient population responds to this drug, then for pharmaceutical companies, the reason for which they develop these drugs largely disappears. After all, if the number of patients is measured in tens or hundreds of thousands, such a drug will receive the status of an "orphan drug" (orphan drug), working only for a very narrow group of patients who are unlikely to be able to create a solvent demand in order to recoup research.
At the moment, biotechnologies are likely to move in the direction of finding universal mechanisms that will effectively suppress cancerous tumors using certain unique mechanisms. Just as an embryo tricks the mother's immune system in order to stay alive, so cancer cells use this mechanism to control immunity. The destruction of this mechanism will not cause any damage to healthy cells, but, most likely, it will help the immune system or some means of immune therapy to cope with cancer. In 2013, in the second phase, for the first time, a GSK drug showed success, which managed to obtain immunostimulating drugs that increased the survival prognosis of patients in combination with various forms of therapy or independently.
6. Glycolysis as an energy sourceAs you know, cancer cells use a completely different way of breathing.
When the immune system tries to kill a particular cell of the body, the death of the cell comes through the destruction of the mitochondria – this is a special organelle, part of the cell that is responsible for energy production. Those cancer cells that were able to turn off the mitochondria or get rid of it, obviously, cannot be killed in this way, so after a few weeks or months after the onset of cancer in humans, almost all cancer cells breathe without mitochondria, using a completely different mechanism for obtaining energy, which is called "glycolysis". Glycolysis is ineffective, so it is not used by healthy cells. Drugs that would turn off glycolysis could leave cancer cells on a starvation ration and kill them either on their own or in combination with other drugs. It is along this path that success has recently been achieved in preclinical trials and in the early phases of clinical trials with drugs that control various forms of cancer metabolism.
There is still no evidence, except for animal trials, that it is this approach or the approach associated with immune therapy that will allow us to someday talk about the possibility of curing cancer patients. However, the fact that from the attempts of the last decades to develop a targeted drug for a narrow group of people against certain markers, researchers are again beginning to move in the direction of finding universal anti-cancer drugs with a broad effect, allows us to hope that sooner or later this disease will be controlled.
About the author:
Peter Fedichev – PhD, Associate Professor at the University of Innsbruck (Austria),
Scientific Director of Quantum Pharmaceuticals.
Portal "Eternal youth" http://vechnayamolodost.ru04.09.2014