Approaches to diagnostics and gene therapy of cancer (T.V. Vinogradova, E.P. Kopantzev, I.P. Chernov)

Currently much attention is paid to development of new generation therapy of cancer. Within the framework of the State program «Priority fields in science and technology in Russia during 2007–2012» our lab participated in the integrated project «Development and production of the prototype of novel and effective therapies and diagnostics of the post-genome generation for use in tumor therapy». The aim of this project was the development and clinical tests of first gene therapy based preparations for treatment of lung and esophagus cancers. The approaches used in this project are based on the fundamental and methodical research performed in the laboratory. The project integrates efforts of the major scientific centers of Russia: Institute of Molecular genetics RAS, Blokhin Cancer Research Center RAMS, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Novosibirsk State University, Institute of gene biology RAS, Gamaleya Research Institute of Epidemiology and Microbiology RAMS, and biotechnology companies Evrogen and Binnofarm. Within the framework of this project the constructions allowing for specific expression of therapeutic genes in tumor cells and systems for delivery of the therapeutic genes into tumors were developed.

Hence, the bases were established for the development and production of novel effective medical preparations and diagnostics based on gene therapy approach and biologically active proteins.

Cancer and development (M.V. Zinovyeva, T.V. Vinogradova, G.S. Monastyrskaya)

Demonstration of the fact that genes that are activated during development of lung and esophagus in embryogenesis are switched off in normal cells when they are being transformed into cancer cells and conversely is one the major achievements of the project. This confirms the hypothesis that process of cancer transformation and progression of normal cells may be compared with embryonal development or self-reproduction and differentiation of stem cells of certain tissues. The genes that express differentially in cancer and development probably play key role in tumorigenesis. Study of such genes allows carrying out a rational choice of therapeutic targets because systems regulating embryonal development and damaged in cancer are most perspective targets.

Modified oligonucleotides (V.K. Potapov)

Development of new methods of production and synthesis of modified oligonucleotides with changed structure of the base or of sugar-phosphate skeleton was the mainstream of the group through the last three years. Working out of approaches to solid phase synthesis of morpholino-analogues of oligonucleotides, which have morpholine ring in their structure instead of ribose, is the most perspective direction of the research. Such analogues are uncharged molecules and resistant to nucleases. They preserve DNA structure and form stable complementary bonds with native oligonucleotides.

Synthesis of oligonucleotides bearing spacers of specified length with thiol group in certain sites is the second direction of the work. These oligonucleotides are used in study of their complexes with integrases of HIV and ASV by X-ray diffraction analysis by prof. Vlodover group (NCI, Frederic).

Microenvironment of the tumor and expression of genes (Pleshkan Viktor, Antonova Dina)

According to modern ideas, the tumor is a complex structure, consisting of the actual tumor cells and cells of the tumor microenvironment. Microenvironment, or stroma, is a cancer associated fibroblasts (CAFs), immune cells, cytokines and other elements. The stroma is necessary for maintenance of a tumor progression, protection and proliferation of tumor cells. The diverse interaction of tumor and stromal cells provides these processes. Different patterns of gene expression are characteristic of tumor and stromal cells. Many of these differentially expressed genes are key to the "tumor-stroma" interaction.

We are studying the CAFs, their main markers, and ways of influencing them as a potential target for antitumor therapy. In our laboratory, several genes with increased expression in the CAFs were identified. We investigate the promoters of these genes for tissue-specific expression in tumor microenvironment cells for use in gene therapy. We also examine the products of genes of the tumor microenvironment and their role in the progression of the tumor and the possibilities of using them to create new antitumor approaches. Thus, we investigate the effect of CTGF connective tissue growth factor on the migration of tumor cells and its relationship to other pathological processes in tumor progression. In our group, experiments are conducted to identify the potential of tumor-associated fibroblasts to act as a target in antitumor therapy. We are ready to work with new students who have the opportunity and desire to work hard on this topic.

Scientific projects

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Igor' Chernov

Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map