Cancer and epigenetics
Epigenetic changes affect the occurrence and development of oncological diseases
Polina Kustova, "Science in Siberia"
Switching on and off certain genes in cancer cells can help in the treatment of such diseases, in particular, several similar drugs have already been developed that affect DNA methylation, histone modification and synthesis of certain microRNAs. In addition, knowledge of the genetic markers associated with certain disease processes can help in prescribing more accurate and effective treatment. It is on these issues that scientists are currently working.
Researcher of the Laboratory of Molecular Mechanisms of Carcinogenesis of the Research Institute of Molecular Biology and Biophysics of the Federal Research Center for Fundamental and Translational Medicine Tatyana Sergeevna Kalinina spoke about the role of DNA methylation and other processes in the initiation and progression of oncological diseases and the prospects for the development of new methods of diagnosis and treatment in the framework of the round table "Translational Medicine in Oncology" (OpenBio-2022).
DNA methylation is the process of turning on and off the activity of certain genes. In tumor cells, its suppression occurs, which leads to the development of oncological diseases. Given the importance of the methylation cycle, Tatiana Kalinina listed drugs aimed at resuming this activity. "Currently, Decitabine is used in medical practice. This drug is an inhibitor of the enzyme responsible for DNA methylation. Its main action is aimed at restoring the expression of tumor suppressors responsible for preventing the transformation of cells into cancer cells. The Swiss drug Azacitidine performs a similar function," the scientist says.
Tatiana Kalinina also mentioned other drugs used today in the treatment of oncological diseases. Firstly, it is the Dutch drug "Vorinostat", which affects the change of histone modification patterns. Histones perform two important functions in the human body: they are responsible for DNA packaging and regulation of transcription levels. "Vorinostat" deactivates histone deacetylase, which leads to the restoration of the expression of tumor suppressors. It is mainly used for the treatment of orphan, very rare diseases. Secondly, these are oligonucleotides aimed either at inhibiting the action of specific microRNAs, or, conversely, restoring their level. Only one drug has a similar mechanism of action today — Patisiran.
The researcher also stressed that the big problem today is the differential diagnosis of thyroid tumor diseases. "In our laboratory, among other things, we are searching for markers that can be used to distinguish adenoma from thyroid cancer. Our scientists have found two microRNAs and four target genes, the expression of which differs significantly in patients with these two diseases. Their choice was not accidental: it is known that the ratio of women and men with thyroid cancer is 3:1. Therefore, we chose microRNAs, among the targets of which there are estrogens and progesterone receptors that respond primarily to female hormones," explains Tatiana Kalinina.
Tatiana Kalinina called the exact diagnosis of the status of the epidermal growth factor receptor HER2-neu in breast cancer at the preoperative stage another significant problem. "The difficulty lies in the fact that in about 20% of cases, the results of immunohistochemical analysis of biopsy and postoperative materials do not coincide. And it turns out that every fifth patient is either undertreated, or, conversely, receives excessive treatment at the preoperative stage. As part of our work, we found two microRNAs that differ with high reliability in patients with a positive HER2-neu status," says Tatiana Kalinina.
The scientist raised the issue of the importance of accurate diagnosis of metastatic lymph node lesions in breast cancer. "The traditional methods of breast cancer treatment used do not allow an accurate diagnosis at the preoperative stage, so it is made after the removal of lymph nodes. In most regions, including Novosibirsk, axillary lymph dissection is performed, which, depending on the stage of the tumor, involves the removal of 10 to 40 lymph nodes. This procedure leads to a number of complications and reduces diagnostic accuracy, because there is a high probability of not getting to the sentinel lymph node, where the tumor cells are located. At the moment, we have found six microRNAs whose expression in cancers differs significantly in patients with and without metastases. Further testing will include a large sample, as well as the use of biopsy material. I hope this will allow us to develop a system for preoperative diagnosis of metastatic lymph node lesions," concludes Tatiana Kalinina.
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