Liquid biopsy: the current state of the issue

Background Liquid biopsy is a promising method of diagnosing malignant tumors. It allows determining the level of free circulating tumor cells – micrometastases, tumor DNA, microRNA and exosomes in blood plasma, as well as detecting various genetic changes. This work included a literature review of current scientific publications on liquid biopsy techniques indexed in PubMed.Objective The aim of the study was to evaluate the efficacy and peculiarities of this technique in comparison with standard methods of morphological verification of oncological diseases, as well as the feasibility of its use in clinical practice. Compared to tissue biopsy LB has the following advantages: simplicity and speed of examination, easy repeatability and low invasiveness, possibility of dynamic monitoring of tumor progression – general clonal transformation as well as the appearance of resistance to treatment. The disadvantages of this method include low sensitivity, difficulty in proper interpretation of biomarkers and determination of their specificity, high risk of false positive and false negative results due to the presence of dormant tumor cells.Conclusion Currently, liquid biopsy analysis in clinical practice requires standardization and continuous validation

The epithelial-to-mesenchymal transition in cancer: pathogenetic features

The epithelial‑to‑mesenchymal transition (EMT) is a cellular biological process, that occurs in a wide range of cells and tissues and is triggered by complex regulatory networks involving transcriptional control with SNAIL, ZEB1, ZEB2, Twist, SLUG, E‑cadherin, vimentin, tumor microenvironment and genetic characteristics. EMT is represented by the multi‑stage development and transformation of cells of the epithelial phenotype into cells that acquire mesenchymal features of various severity. These quasi‑mesenchymal cells are characterized by stemness, tumor heterogeneity, increasing invasiveness, drug resistance and a tendency to distant metastasis, which leads to the proliferation of neoplastic cells, tumor dissemination and initiation of metastasis, which induces the therapy resistance and the oncological recurrence.This review is based on the latest scientific publications about the EMT phenomenon, indexed in PubMed. The aim of the study was to evaluate the biochemical and molecular pathogenetic mechanisms of EMT and the effect of EMT markers on the progression of neoplastic processes and the effectiveness of the treatment. Nowadays the proper EMT scheme that combines all the molecular transformations of sells with quasi‑mesenchymal phenotype doesn’t exist. But analyzing the features of this cellular program, we can find the proper therapy, that could be able to suppress the plasticity of cancer cells, prevent EMT induction by blocking contextual signals, and induce mesenchymal‑epithelial transition. All these aspects will lead to the reduction of the risk of tumor dissemination and the increase of the effectiveness of cancer treatment

THE ROLE OF HUMAN PAPILLOMAVIRUS IN DEVELOPMENT OF OROPHARYNGEAL CANCER

This article provides review of foreign literature on the problem of HPV-associated oropharyngeal cancer incidence. Epidemiological researches demonstrate increase of incidence of oropharyngeal squamous cell carcinoma (OPSCC) especially among white men of middle age. Such growth of oropharyngeal cancer incidence is associated with human papilloma virus type 16 (HPV 16). The p16 - protein expression is the marker of HPV DNA integration into human nuclear DNA. It is suggested that detection of tumor HPV-status can predict prognosis and develop preventive measures

TREATMENT OF HEAD AND NECK SQUAMOUS CELL CARCINOMA ACCORDING ON THE SPECIFIC MOLECULAR FEATURES OF THE TUMOR (A LITERATURE REVIEW)

Despite the achieved progress in radiotherapy, chemotherapy, and surgery, head and neck squamous cell carcinoma (HNSCC) still remains the sixth most common cause of death from cancer worldwide. The division of HNSCC into 2 large groups with different survival rates is a significant achievement made during the last decades in cancer research and treatment of head and neck cancer. In 45 % – 90 % of cases, oropharyngeal squamous cell carcinoma is presumably associated with human papillomavirus (HPV). A recent whole-exome sequencing study on HNSCC helped to develop new principles of treatment that will allow to increase the effectiveness of conventional therapy. The study demonstrated that inactivating mutations in the p53 gene trigger carcinogenesis. The majority of tumors have such mutations that inactivate the p53 tumor suppressor gene. According to the results of sequencing, HPV-positive and HPV-negative tumors have completely different mutation profiles. Intratumoral heterogeneity should be taken into account when implementing new treatment approaches. We present an overview of studies published between 1989 and 2014. Current review briefly describes molecular mechanisms of carcinogenesis in HNSCC in the light of genetic and biochemical features of the tumor, paying particular attention to the most significant scientific achievements in this field. Moreover, we outline the advancements of wholeexome sequencing in HNSCC and give an overview of recent studies devoted to new therapeutic approaches. The process of carcinogenesis in HNSCC is often initiated by tumor suppressors. In this case, the development of target-based drugs is problematic. Target therapy focused on the ways of tumor growth suppression is a much more serious challenge than inhibition of oncogenic signals, because it requires reactivation of tumor suppressors and restoration of their functions, which is more difficult than conventional chemical and biological blockage. Poor survival of patients with HNSCC, which is usually associated with a small size of recurrent tumors, their latent growth, and localization in various anatomical areas, shows that there is an urgent need for developing new therapeutic approaches for the disease. The study was aimed to analyze specific molecular features of head and neck tumors and to explore the opportunities of providing personalized care for these patients