How new cancer drugs are being created
"Science guides us in drug development"
Nadezhda Markina, "Newspaper.Ru"About new treatments for complex forms of cancer, accelerated drug development and an unsuccessful drug to the correspondent of "Gazeta.
Ru" said Alessandro Riva, author of more than 100 scientific publications in the field of oncology, head of the global Department for Cancer Research and Medical activities of Novartis.
– When you start developing a new cancer drug, how do you determine which type of cancer you are going to fight? Do you choose the most common or the most intractable types of cancer?
– Our decision is not based on the frequency of the disease, it is based on our knowledge of the ways of developing various types of cancer and the possibility of developing a therapy for it. In other words, when developing new drugs, we are guided by science to a greater extent than the prevalence of the disease.
– How do you choose targets for the action of drugs?
– Targets are selected based on knowledge of the mechanisms of development of different types of cancer and the prognostic value of this target in relation to the disease. Then we develop a model of the drug's action and try to assess how much better the result of a particular agent is for patients.
– A cancerous tumor is known for changing rapidly. How do you overcome this problem?
– We need to monitor the resistance of the tumor that may occur during treatment. But we can't do a biopsy during the whole treatment. Therefore, we are trying to develop surrogate methods that allow us to monitor how mutations that lead to resistance arise. In order not to do a multiple biopsy, we do not analyze the tumor, but the blood.
– How does this method work?
– We know about the existence of some kind of tumor marker. What are we trying to do? We look at the same marker in the blood plasma and compare the presence of this marker in the tumor DNA and in the DNA from the blood. And in this way we determine what happens to the tumor and how it reacts to medications. This is one of the ways that allows us to avoid multiple biopsies, because a biopsy is an invasive diagnosis, and patients do not want it. But with this approach, new horizons are opening up before us. We can offer the patient new therapy options. If we see the result of this treatment, we can think about the next step in the treatment of the patient.
– You are talking about a personalized approach to cancer therapy. Does this mean that your medications do not work effectively on all patients, but on some part of them?
– Yes, a personalized approach involves the selection of patients with a specific genotype, which reduces the time to develop new compounds. Fewer patients are required, and thus, from a statistical point of view, we gain an advantage. It doesn't take a large number of patients to prove that the medicine works for a select group.
– Of the many candidate substances that you started working with, what proportion of them went through the entire development chain and were registered as new medicines?
– We have more than 20 connections. It will take a very long time to quote and name them. They are aimed at the main biochemical pathways that play a key role in the development of a cancerous tumor. I can list several: PI3K, RAS, RAF, mTOR, ALK.
– Tell us about your method of training T-lymphocytes to fight cancer cells.
– The concept boils down to using the patient's T cells to kill malignant B cells. What are we doing? We extract T cells from the patient's blood, send them to the laboratory, and they are modified there. A modified lentivirus is added to them, which contains the CD19 lymphocytic antigen. And thus it is transmitted through the virus to the T-cell. After that, the T cell can present this CD19 antigen on its surface. And when we put these T cells back into the patient's body, they multiply and recognize malignant B cells that have CD19, and thus they are killed.
One of the important advantages of this method is that the modified T cells remain in the patient's blood, continue to multiply and recognize malignant B cells as soon as they appear. While chemotherapy drugs, which are quite toxic, should be given to patients for a long time. And at some point, the treatment is stopped for safety reasons, because the patient simply can no longer withstand such treatment. And in this case, if you injected the patient with altered T-cells, they remain in the body forever.
– You have recently informed the society that your drug afinitor in clinical studies has not shown an increase in life expectancy in patients with hepatocellular carcinoma. Were you upset by this result?
– Of course, we were disappointed. First of all, because of the patients, because this is a very aggressive disease. We developed this clinical trial for patients who were not helped by anything at all. We don't know why the athenitor didn't work. We have taken two more samples from the primary tumor and are trying to see if patients could get some benefit from afinitor or not. Although we planned clinical trials based on reliable biological data, but something didn't work. We don't know why yet. But we continue scientific research to answer this question.
Portal "Eternal youth" http://vechnayamolodost.ru10.09.2013