Cancer is one of the most common diseases worldwide, and its treatment is associated with many challenges such as drug and radioresistance and formation of metastases. These difficulties are due to tumor heterogeneity, which has many causes. One may be the cell fusion, a process that is relevant to both physiological (e.g., wound healing) and pathophysiological (cancer and viral infection) processes. This literature review aimed to summarize the existing data on the hybrid/atypical forms of circulating cancer cells and their role in tumor progression. For that, the bioinformatics search in universal databases, such as PubMed, NCBI, and Google Scholar was conducted by using the keywords “hybrid cancer cells”, “cancer cell fusion”, etc. In this review the latest information related to the hybrid tumor cells, theories of their genesis, characteristics of different variants with data from our own researches are presented. Many aspects of the hybrid cell research are still in their infancy. However, with the level of knowledge already accumulated, circulating hybrids such as CAML and CHC could be considered as promising biomarkers of cancerous tumors, and even more as a new approach to cancer treatment.

Purpose of the study: to assess the relationship between atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid of ovarian cancer patients and the levels of cancer markers, such as CA125 and HE4, and the tumor grade. Material and methods. The study included 48 patients with newly  diagnosed ovarian cancer (42 patients with stage Ic–IV ovarian cancer and 6 patients with borderline ovarian tumors (Bots). The age of the patients ranged from 36 to 76 years. the study material included ascitic fluid and blood samples. the presence of atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid was identified by laser multicolor flow cytometry. The levels of CA125 and HE4 markers were measured by ELISA. Results. The number of EpCAM+CD45+ cells in ascitic fluid of patients with serous ovarian carcinoma was 1.02 (0.30; 2.68) cells/µl (0.55 (0.03; 4.51) cells/µl in patients with low-grade serous carcinoma (LGSC) and 1.36 (0.41; 2.68) cells/µl in patients with high-grade serous carcinoma (HGSC). The number of EpCAM+CD45+ cells in ascitic fluid of serous ovarian carcinoma was shown to have a strong  correlation with СА125 and HE4 levels in blood serum (R=0.60; р<0.01 and R=0.34; р=0.05, respectively). In the LGSC group, there was a strong direct  correlation between the number of EpCAM+CD45+ cells in ascitic fluid and the levels of CA125 and HE4 markers in blood serum (R=0.93; p<0.01 and R=0.68; p=0.03, respectively). No differences in the levels of EpCAM+CD45+ cells in ascitic fluid and CA125/ HE4 markers in blood serum between patients with HGSC and LGSC were found. the levels of atypical/hybrid forms of cells in ascitic fluid and CA125/ HE4 markers in blood serum were  significantly lower in patients with Bots than in patients with serous ovarian carcinoma (p=0.02 for EpCAM+CD45+ cells and p<0.01 for СА125/ HE4 levels). Conclusion. The relationship between the number of EpCAM+CD45+ cells in ascitic fluid and the levels of CA125 and HE4 markers in blood serum of patients with serous ovarian carcinoma was found. However, no differences in the levels of EpCAM+CD45+ cells in ascitic fluid and CA125/ HE4 markersin blood serum between patients with HGSC and LGSC were observed.