The incidence of cervical cancer is gradually shifting to an earlier age range, creating many problems, such as a decrease in life expectancy, working and fertile periods, and an increase of social and economic burden on the healthcare system and the state as a whole. Screening with liquid-based cytology can help to diagnose dysplasia and the initial cancer manifestation in situ. The purpose of this article is to analyze the possible advantages of liquid-based cytology for mass screening.
The review considers modern cancer vaccines consisting of autologous whole cells, dendritic cells loaded with autologous tumor-specific antigens, or plasmids, which lead to antigen expression and immune activation after repeated exposure. Each vaccination strategy can be supplemented with various immunomodulatory agents. Engineering autologous immunotherapy of tumor cells is an approach to restoring the effector function of T cells. Other tumor-associated antigens (TAAs) are also of interest in ovarian can cer. Adoptive immunotherapy is based on infusion of autologous or allogeneic tumor-targeted immune cells that have been expanded and/or activated exvivo. Adoptive immunotherapy can be based on antigen-dependent (innate immunity, for example, natural killer (NK) and cytokine-induced killer (CIK) cells) or antigen-independent (adaptive immunity, for instance, TILs, chimeric antigen receptor (CAR) T cells) strategies. NK cells can kill tumor cells without prior sensitization and play an important role in tumor immunosuppression. Adoptive T-cell immunotherapy, CAR-T-cell immunotherapy, allows combining antigen specificity through conjugation of a specific antibody with T-cell activating properties in a single fused molecule. CARs bypass the immune mechanism of cancer cell release as they endow T-lymphocytes with cytotoxic effector properties. In order to reduce mortality and improve prognosis, further study and refinement of immunotherapeutic strategies for the treatment of ovarian cancer is required.
The review considers modern immunotherapy for ovarian cancer with immune checkpoint inhibitors that interfere with the ability of the tumor to activate control proteins on the surface of T-cells, preventing cancer from evading the immune response and allowing the immune system to generate an antitumor response. The presence of spontaneous tumor-specific T-cells in cancer patients is a factor in creating ways to overcome the blockade of the immune system's ability to inactivate tumor cells. The use of immunotherapy with monoclonal antibodies makes it possible to influence the checkpoints of immunity, leads to the activation of the immune response, blocking the interaction of the PD-1 protein with the corresponding PD-L1/PD-L2 ligands and the attack reaction on tumor cells. The antitumor effect is achieved by releasing effector T-cells, reducing the function, number and suppressor activity of intratumoral Tregs. For antitumor drug therapy, anti-PD-1 and anti-PD-L1 monoclonal antibodies are used. This therapy is accompanied by various adverse events that are associated with the ability of PD-1 to interact with CD80 and the second PD-L2 ligand. Encouraging results of anti-PD-1/PD-L therapy in ovarian cancer resistant to platinum-containing chemotherapy may become an additional option in the treatment against the progression of ovarian cancer.
Aim to study the frequency of BRCA1/2 gene mutations , the efficacy of ovarian cancer therapy depending on the presence of BRCA1/2 mutations as well as the efficacy of olaparib maintenance therapy in BRCAassociated ovarian cancer.Material and Methods. The retrospective analysis included 355 patients with high-grade, stage I–IV serous ovarian cancer. The examination for a mutation in the BRCA1/2 gene was carried out within the framework of the program “Improvement of molecular genetic diagnostics in the Russian Federation in order to increase the effectiveness of antitumor treatment”.Results. Mutations in the BRCA1/2 genes were detected in 98 out of 355 (27.6 %) patients. Mutations of the BRCA1+ gene were detected in 62 out of 230 patients with ovarian cancer of stages IIIC–IV (27.0 %), the BRCA2 gene – in 9 out of 230 (3.9 %). In ovarian cancer of stages III–IV, BRCA gene mutations were absent in 159 of 230 (69.1 %) patients. The median time to progression in stages III–IV of the disease with a mutation in the BRCA1 gene was 22.0 months, in the BRCA2 gene – 27.0 months, in patients without mutations in the BRCA1/2 genes – 17.0 months, median life expectancy – 70.0; 65.0 and 45.0 months, respectively. Patients with serous ovarian carcinoma of high-grade I–IV stages with the presence of mutations in the BRCA1/2 genes were divided into two groups. The first group (6 out of 26 patients, 23.1 %) consisted of patients with stage IIIC–IV high-grade serous ovarian carcinoma, who received olaparib as maintenance therapy after the 1st line of chemotherapy, the second group (20 out of 26 patients, 76.9 %) were patients with stage I–IV high-grade serous ovarian carcinoma, who received olaparib in maintenance mode after 2 or more lines of chemotherapy.Conclusion. The presence of BRCA1/2 gene mutations significantly increased the median life expectancy of patients with stage IIIC–IV serous ovarian cancer, and primary cytoreduction significantly improved both overall survival and survival to progression in this group of patients. Maintenance therapy with olaparib is more appropriate after the 1st line of treatment than after subsequent ones.
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