Genetics is the key to cancer treatment
Such results will help to achieve the study of genetic changes occurring in cells during the development of cancer.
Last week, the VII Russian Conference "Malignant Lymphomas" was held in Moscow. One of its participants, a world-renowned specialist in the study of cancer genetics, professor at Ohio State University and director of the human cancer genetics program Carlo Croce told the correspondent of "Gazeta.En" about his vision of the future of cancer treatment and the reasons for the effectiveness of science in the USA.
– What do you think is the most successful approach to cancer treatment in the future?
– I believe that if we really want to learn how to successfully treat cancer, we need to learn how to identify critical genetic changes that occur in cells during the development of cancer.
Moreover, the most important changes are those that occur at the earliest stages of the development of the disease, when it is still impossible to diagnose it with existing methods. Because early genetic changes will be present in the vast majority of cancer cells, but later mutations will no longer be universal, they will be present only in a part of them.
– Is there, at the moment, a clinical therapy created on the basis of this approach?
– It is not yet universal, but it has already been developed for a number of cancers. The fact is that we can already "target" a small part of such genetic changes. But, of course, not everything yet. For example, it is already possible to treat chronic Myelogenous leukemia (Chronic Myelogenous Leukaemia, CML – the most common form of blood cancer – approx. "Newspapers.Ru». In this disease, a certain enzyme, tyrosine kinase, is activated. And we can target this enzyme with a drug. That is, we can make, it's very simple, an enzyme inhibitor. Many years ago, it seemed difficult. Now it's very simple. And the percentage of cure is very large. When the critical stage is the activation of an enzyme, then we can create a drug, this is fundamentally possible. However, we have to work with the earliest genetic change. If we purposefully act on the earliest genetic change, with just one drug we can defeat the disease. At the same time, complete remission is observed in the statistical majority of patients without any side effects! After some time, the disease may return. However, this will again be a mutation in a certain molecule. This means that the molecule has become resistant to the action of the developed drug – and this is even stronger confirmation that genetic changes are the key to the development of cancer.
– How to deal with the disease in such cases?
– This is the next level of work. When we can develop not one, but several drugs that act on this goal plus an additional goal, we will be able to completely treat the disease, the same CML. This is fundamentally possible now, such drugs are the near future. Another question is that for some cancers we know the goal, but it is not so easy to develop a cure for it. That is, it is not an enzyme for which you just need to create an inhibitor. Although this is not a verdict. For example, the protein factor Bcl-2, suppressing apoptosis (the phenomenon of programmed cell death), involved in the development of melanomas, breast, prostate, lung cancers, is not an enzyme. But it can also be "turned off" by the action of a medicinal drug. However, such a drug is very difficult to create, it takes years.
– Then maybe other approaches to cancer treatment should be developed – proton therapy, micro-RNA therapy?
– Not at all. Such targeted therapy is more effective, it interrupts the disease at a key stage for its development, it does not cause side effects.
Proton therapy affects the tissue less strongly than conventional radiation therapy or chemotherapy, but this is already a late-stage treatment. And our goal is to stop cancer in the bud, when it has not yet really begun to infect cells. And this is not a tumor treatment as such. It turns out only to kill cancer cells, but not to eliminate the cause of cancer. It is good when it turns out to focus the radiation better to avoid tissue damage. But this is not a treatment as such. Micro-RNA is also targeted therapy, but its clinical application requires years of research, many years.
– What are the stages of development of targeted cancer therapy in your center?
– At the first stage, we identify the genes responsible for the development of a particular type of cancer. In order to accurately localize the desired variation of the gene, model studies are conducted on mice. Then begins the development of a drug, a chemical that can affect the found target. It takes, sometimes, several years. Therefore, long-term tests are needed to confirm that this medicine works and works as it should. It's a long process.
– What is the difference between early, preventive cancer treatment and conventional methods?
– Now cancer is detected at a late stage of tissue damage. In this case, it is no longer possible to treat it with medications, surgical or other intervention in the body is necessary. Why? Because there is no longer one "broken" enzyme. In tumor cells, the whole enzyme machine does not work correctly, mutations accumulate at a rate hundreds of thousands of times higher than normal. Therapeutically, nothing can be done, the cancer cell will develop resistance against any drug, mutating at such a rate.
Therefore, the strategic task is to identify precancerous genetic mutations at the earliest stage. Sometimes mutations begin 20-30 years before the immediate development of the disease. And at such an early stage, cancer can be treated. If, of course, we effectively register "dangerous" genes.
– How will they be examined for such a "hidden cancer" in the future?
– I think it will be a preventive examination – just a blood test. You donate blood, let's say, once every six months. An express analysis is carried out for biomarkers, the presence of which in the blood indicates an early stage of the development of a particular type of cancer. If it turns out that there is a danger of developing the disease, you immediately receive preventive treatment. This is what we are striving for, but it will not happen so soon.
– And what can be done now?
– Now we can achieve complete remission only for a limited range of diseases. Progress is moving, but in small steps, not as fast as we would like. However, for many patients whom we cannot cure completely, we can significantly prolong their lives, improve their quality of life, which is also extremely important.
– How do you think it is possible to ensure the effectiveness of scientific work, what are the conditions for the emergence of great scientific discoveries?
– There are several conditions. First of all, any scientific center needs highly educated, creative-minded young people who can bring new ideas. Strong funding is needed so that financial difficulties do not stop researchers from implementing ideas. My center spends huge amounts of money every year, it can't do without it. Of course, we also need a strong older generation that will train and guide the young. An atmosphere of constant verification of ideas should be created, everything should be questioned and the most thorough independent verification. In a dispute, the truth is born.
One of the reasons for the scientific success of the USA is their university system, where all these conditions are met. The secret of success is investing in brains and giving young people the opportunity to realize their ideas. There is no such thing in Europe – that's why I left Italy so quickly. The same problems are also being raised by Russian colleagues at the conference. There are no such opportunities. The bureaucracy is very strong, and it hinders scientists. There is bureaucracy in the USA, too, of course, but it is much easier. All my funding is grants, which I have to write constantly. In general, only 10-15% of the applications received are funded. On the one hand, it provides a highly competitive environment. On the other hand, it is difficult to get a grant for the implementation of a truly revolutionary idea. Grants get ideas that look reasonable, realistic. But when an idea looks realistic, it's not revolutionary! Therefore, in order to develop a truly new direction, we often receive funding for something simpler, more understandable. Part of the money goes to the development of a new idea, and if it is successful, we are already fighting for funding with these results in our hands. It doesn't work out any other way yet.
Portal "Eternal youth" http://vechnayamolodost.ru03.11.2010