14 July 2014

Targeted drugs in oncology

5 facts about various targeted medications,
types of breast cancer and the future of targeted medicine

Nikolay Borisov, Post-scienceThe approach to the cure of such a complex disease as cancer can already be based on the analysis of the interaction of various proteins and genes that are combined into complex networks.

Activation of various proteins included in such networks causes the cell to divide and metastasize uncontrollably, that is, to turn from normal to cancerous.

1. A variety of antitumor drugsBy the nature of the effect, antitumor drugs can be classified into four classes.

The first is monoclonal antibodies (mabs, monoclonal antibodies), that is, protein molecules or complexes of protein molecules that are produced by the immune system in response to some antigens-oncogenes. Such monoclonal antibodies bind to oncogenes and suppress their activity.

A variety of such monoclonal antibodies are the so-called killer monoclonal antibodies, or killermabs, which are complexes of a cytostatic agent that kills a cell and an antibody with an increased affinity (affinity) for this antigen.

If monoclonal antibodies are macromolecules, then another class of targeted antitumor drugs – nibs, or kinase inhibitors – are low-molecular compounds. As a rule, these compounds reduce the activity of some specific oncogenes that affect the formation of a signal in the cell, causing the cell to divide uncontrollably.

The fourth class of targeted drugs in oncology are, on the contrary, not inhibitors, but activators, but no longer oncogenic, but oncosuppressive (suppressing) signaling pathways that cause, for example, necrosis, apoptosis or cell differentiation. Such drugs include various stimulants of necrosis, apoptosis or differentiation.

2. The peculiarity of targeted drugsAll these drugs are called targeted, or targeted, because they act selectively on some of the incorrectly expressed, overexpressed or incorrectly arranged, that is, mutated oncogenes.

Such drugs are usually prescribed in clinical practice by the method of immunohistochemical examination of a tumor biopsy. During an immunohistochemical study, a sample of malignant tissue is taken from the tumor and then the expression level of some key oncogene is determined using the appropriate antibody.

3. Types of breast cancerOne of the first and most expensive targeted anticancer drugs – Herceptin, or Trastuzumab – appeared at the very end of the XX century, was produced by Roche and was intended for the treatment of a special form of breast cancer.

Scientists in the last century identified two types of hormone-dependent breast cancer: estrogen-dependent and progesterone-dependent. The third type, the most malignant, was first designated by doctors as "neither one nor the other". Then it turned out that the development of this third type of breast cancer is responsible for the so-called heregulin, or unregulated receptor, doctors call it HER2 / neu, biologists it is known by the international name ErbB-2. It is a relative of the epidermal cell growth factor receptor, but normally determines the growth of nerve tissue. In HER2-dependent breast cancer, it is pathologically expressed, constantly signaling, which causes the cell to divide.

4. How was the first targeted medicine obtainedThe first drug Trastuzumab was very expensive and difficult to produce Due to the fact that this drug was produced by the embryonic cells of a mouse, which was designed by genetic engineering methods so as not to contain unnecessary antigens for humans.

He was, as it were, artificially humanized, that is, the most unlike human genes were removed from him and replaced with human ones. In the second week of embryonic development, this embryo produced monoclonal antibodies against HER2-dependent breast cancer.

As a result, the technology was very expensive, the medicine cost about as much as an apartment in Moscow, and the effectiveness even when prescribed according to the indications detected during the immunohistochemical study was very low, no more than 30%.

5. Prospects of targeted medicineOf course, Herceptin, or Trastuzumab, is already quite an old drug with more than 14 years of history; for modern targeted medicine, this is a very solid experience.

Currently, there are more than a hundred targeted drugs registered and approved for medical use in various countries of the world. At the stage of preclinical and clinical trials there are hundreds of new mabs and cheaper than mabs, nibs. How can doctors develop such a number of medications and prescribe the drug that is most suitable for this patient?

Fundamental biology and bioinformatics come to the doctor's aid. In a joint project of three leading scientific and medical institutions in Moscow, such as the A.I. Burnazyan Federal Medical Biophysical Center, the D. Rogachev Center for Pediatric Hematology, Oncology and Immunology and the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, a system-biological platform was created for prescribing targeted antitumor drugs based on the results of a microchip study of the patient's entire transcriptome a person. This method uses the results of a survey of the expression levels of tens of thousands of genes, among which the majority are either oncogenes or oncosuppressors. Now we can say that personalized medicine is not a dream of philosophers, but a strict medical, biological and mathematical technology.

About the author:
Nikolay Borisov – Doctor of Technical Sciences, Burnazyan Federal Medical Biophysical Center.

Portal "Eternal youth" http://vechnayamolodost.ru14.07.2014

Found a typo? Select it and press ctrl + enter Print version