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We analyzed associations of polymorphic markers of DNA repair genes (XRCC1, ERCC2), cell cycle control genes (TP53, MDM2, and CDKN1A), methylation of promoter region, and mutation 5382insC of BRCA1 gene in ovarian cancer with effectiveness of platinumbased chemotherapy assessed by the median of progression-free survival time for markers of DNA repair genes and by relapse risk for all studied markers. An increase in the median of progression-free survival time for carriers of the Gln allele (р=0.025) and Gln/Gln genotype (р=0.022) of the Gln399Arg XRCC1 was observed during the 19-months period after chemotherapy. In carriers of C/C genotype of 5382insC mutation of BRCA1 gene (n=6), no relapses were observed (р=0.035), while 17 of 49 patients without this mutation developed relapses. Of 14 patients with BRCA1 gene function inactivation due to promoter methylation or the presence of the C/C genotype of 5382insC, one relapse was observed (p=0.033). Multivariate analysis revealed an association of markers of the XRCC1, TP53, MDM2 genes, BRCA1 gene inactivation, and type of surgery with the risk of relapse during the follow-up period up to 19 months after the end of chemotherapy (р≤0.0007).

The Russian economy's long-term growth is inextricably linked to an appealing and efficient investment process, without which it is impossible to upgrade output structurally and qualitatively, build market infrastructure, and boost local competitiveness. The pressing issue of adequate investment tools necessitates an active search for viable sources for domestic economy demands, which concretizes the problem of mobilizing the state's internal resources - the population's savings. According to the experience of countries with a high degree of economic development, population savings are the primary source of establishing the resource basis for ensuring long-term economic growth and development. The function of the domestic financial market in the process of converting savings into investments is examined in this article. It has been established that there is a link between the financial market and the investment process. Theoretical components of the essence of savings and how they are transformed into investments are exposed. The impact of household financial investment volumes on the country's economic development indicators is studied and the dynamics and structure of population savings in Russia. The issues surrounding the conversion of savings into investments are recognized and the directions for intensifying it to maximize the financial potential of savings for the implementation of investment programs.

We studied the association of polymorphic markers of cell cycle control genes (Arg72Pro of the TP53 gene, T(-410)G of the MDM2 gene, and Ser31Arg of the CDKN1A gene) in ovarian cancer and progression-free survival following platinum-based chemotherapy. Tumor tissue samples obtained from 49 patients who had undergone chemotherapy were examined. Patients received standard platinum-based chemotherapy and were observed until disease progression. Polymorphic markers of genes were evaluated by PCR-RFLP and real-time PCR. In patients carrying the G allele of the T(-410)G marker of the MDM2 gene, a decreasing trend was observed in median progression-free survival. An increase in the median progression-free survival was observed in carriers of the Pro allele of the TP53 gene (p=0.045). Furthermore, a stronger association was noted with carriers of the minor Pro/Pro homozygous genotype relative to the Arg/Arg genotype (p=0.007). In the subgroup of patients who underwent optimal or complete cytoreductive surgery, carriage of the minor Arg allele of the Ser31Arg marker (CDN1A gene) was associated with a decrease in the median progression-free survival time (p=0.004).

The involvement of axillary lymph nodes is one of the most important prognostic factors, significantly affecting the treatment strategy for early breast cancer (BC). The risk of axillary lymph node metastases depends directly on a number of factors (age of women, size of tumor, presence of lymphovascular invasion and biological characteristics of cancer). The evaluation of regional lymph node status in patients with early BC includes the clinical examination of regional zones and the ultrasound study (US), using these methods can help to study lymph nodes shape, borders, margins and structure. The sensitivity of ultrasound in the evaluation of regional lymph nodes status directly depends on the biological subtype of the tumor; the minimum level of ultrasound sensitivity in the evaluation of lymph nodes status is detected for luminal HER2-negative cancer (less than 40%), and maximum sensitivity is detected for triple negative and HER2-positive subtypes (6871%). Clinical examination and modern ultrasound are the most accessible methods for the evaluation of regional lymph nodes status, but the possibility to misjudge metastatic process can be detected in 1/4 of patients. Verification of the diagnosis in the preoperative phase (fine-needle aspiration biopsy/core-needle biopsy under ultrasound guidance) allows minimize the number of errors for the regional staging. The sentinel lymph node biopsy (SLNB) is the gold standard of regional treatment in patients with early stage BC, nowadays. The randomized trials (NSABP B-32, ACOSOG q0011) show the safety of recession of performing regional lymph node dissection in favor of SLNB not only in case of clinically negative lymph nodes, but also in patients with metastases in 2 sentinel lymph nodes, upon condition that organ-conservative treatment and subsequent radiation therapy will be used. High-quality regional staging, the choice of the therapeutic algorithm in accordance with the biological characteristics of carcinoma, the application of the most effective modern drug regimes, the optimal radiation therapy allow not only minimize the extent of surgery, but also achieve high long-term survival results, provide excellent functional results and high quality of life in patients with the involvement of axillary lymph nodes.

Aim. Eribulin is an active cytostatic, associated with a wide range of mechanisms of antitumor effects, but eribulin efficiency and safety in patients with breast cancer (BC), associated with cerebral metastases are still poorly understood. Materials and methods. We analyzed the combined Russian experience of eribulin application in BC patients associated with brain metastases; the analysis included 459 Russian women with advanced BC who had received at least 2 course of eribulin during the period from 2014 to 2018; 35 of 459 patients had brain metastases (40.0% - luminal HER2-negative subtype, 31.4% - triple negative subtype and 28.6%h - HER2-positive BC). The median age was 52 years (39 - 80 years of age). In most cases, the patient had two or more metastatic brain lesions (68.6%; the median was - 3); brain radiotherapy was used in 62.8% of patients before eribulin treatment and in 5.8% of patients was held stereotactic radiation therapy during eribulin chemotherapy. We analyzed the efficiency of eribulin application (the therapy continued until disease progression, the development of unacceptable toxicity, or impossibility to apply the drug for any other reason). Results. The results showed that clinical efficacy (objective response rate + stabilization of disease lasting for more than 6 months) was 48.6%: partial response - in 20% of patients and stabilization of disease - 62.9%; tumor growth control was in 82.9%. Median PFS in all group of patients with brain metastases was 4.1 months and was similar to median PFS in patients who received radiotherapy before eribulin treatment or without eribulin - 4.1 vs 3.47 months; p=0.798. Conclusions. The application of eribulin in BC patients with brain metastasis are absolutely justified, the drug demonstrates the efficiency in a retrospective analysis in a Russian population. The determination of the optimal algorithm for the treatment of patients with metastatic BC associated with brain metastasis requires a multidisciplinary approach and further research.

Ovarian cancer (OC) is the fifth most common cancer in women in developed countries. Despite advances in treatment of epithelial OC: improving techniques and increasing aggressive surgery, the appearance of new cytostatics, targeted drugs, - the overall survival (OS) rates are unsatisfactory (the overall 5-year survival is 38%) and there is still an urgent need in development of new therapeutic agents to improve the results of treatment women with this disease. Olaparib is the first poly (ADP-ribose) polymerase (PARP) inhibitor, which demonstrates the high efficacy of treatment patients with OC associated with mutations in the BRCA genes. And olaparib is approved as a maintenance monotherapy in the treatment of women with platinum sensitive recurrent BRCA-associated OC. This review deals with the information concerning the efficiency and toxicity of olaparib, showing practical guidance on the application. The article focuses on the toxic effects of the drug, which can occur during olaparib therapy, and shows the guidance on management of the disease. Nausea, vomiting, fatigue and anemia are the most commonly reported side effects of olaparib application in clinical studies. Side effects are usually recorded in mild to moderate degree and nondurable. Using proper application and timely monitoring for side effects one can control many toxic actions.

The development of cytostatic therapy in the treatment of ovarian and cervical cancer has resulted in a deadlocked situation. Thus, the basic aim of the investigations was to examine the biological basis of these diseases, last years. Angiogenesis is one of the main factors of the tumor microenvironment, associated with tumor growth and metastasis. In this regard, new drugs that work by inhibiting angiogenesis have started to appear. One of the first drugs studied in randomized phase III studies was bevacizumab. The application of bevacizumab demonstrated the significant increase both in progression free-survival and life expectancy in high-risk group of patients with ovarian cancer and in patients with recurrent and advanced cervical cancer.

The treatment of patients with ovarian cancer remained unchanged over the past years: cytoreductive surgery and platinum-based chemotherapy regardless of the histological type of the tumor. A deeper understanding of ovarian cancer biology has paved the way to developing targeted drugs; the most studied are bevacizumab and olaparib (Lynparza) - the first among PARP inhibitors, which has been recently approved in the world and in Russia. Olaparib demonstrated a statistically significant efficacy in the treatment using supportive regimen in patients with recurrent platinum-sensitive ovarian cancer after successful platinum-based chemotherapy and with the presence of BRCA1/2 mutations and all these characteristics would significantly change the course of the disease in this group of patients.

In recent years, the main scientific directions concerning ovarian cancer have been associated with the attempt to individualize the treatment based on prognostic and predictive molecular biological markers. The damage in BRCA1 and BRCA2 genes is identified in 10-15% of ovarian cancer cases. The main function of BRCA proteins is responsibility for repairing double-strand break in DNA by a mechanism of homologous recombination. The result of BRCA gene dysfunction is BRCA-associated DNA damage repair mechanism. As a result, these tumors can be extremely sensitive to DNA-damaging cytostatic agents - such as platinum-based drugs. Several studies show the better survival rates of patients with BRCA mutations in comparison with sporadic ovarian cancer. The information concerning the course of disease and treatment characteristics of patients with ovarian cancer associated with BRCA1, 2 mutations in the Russian population of patients is extremely limited.

In recent years, the main scientific directions concerning ovarian cancer have been associated with the attempt to individualize the treatment based on prognostic and predictive molecular biological markers. The damage in BRCA1 and BRCA2 genes is identified in 10-15% of ovarian cancer cases. The main function of BRCA proteins is responsibility for repairing double-strand break in DNA by a mechanism of homologous recombination. The result of BRCA gene dysfunction is BRCA-associated DNA damage repair mechanism. As a result, these tumors can be extremely sensitive to DNA-damaging cytostatic agents - such as platinum-based drugs. Several studies show the better survival rates of patients with BRCA mutations in comparison with sporadic ovarian cancer. The information concerning the course of disease and treatment characteristics of patients with ovarian cancer associated with BRCA1, 2 mutations in the Russian population of patients is extremely limited.

Introduction. High incidence of stage III-IV cervical cancer and high recurrence rate after treatment causes scientific research of alternative approach in patient’s treatment. Objective - improvement results of treatment patients with locally advanced cervical cancer (LACC). Materials and methods. 101 patients with T2b-3bN0-1M0-1 cervical cancer (M1 - paraaortic lymph nodes metastases by radiologic exam) received concurrent chemoradiation therapy followed by adjuvant chemotherapy (CT). External-beam conformal radiation therapy (EBRT) on pelvic and regional lymph nodes 50 Gy (25 fractions) with weekly chemotherapy: arm A - cisplatin 20 mg/m2 + paclitaxel 30 mg/m2, arm В - cisplatin 20 mg/m2 + irinotecan 20 mg/m2, arm C - cisplatin 40 mg/m2. Brachytherapy 30 Gy (4 fractions) following ERBT. In arm A and В after chemoradiation therapy patient received 2 cycles of adjuvant CT: paclitaxel 175 mg/m2 + cisplatin 75 mg/m2 every 3 weeks or irinotecan 65 mg/m2 on day 1 and 8 + cisplatin 75 mg/m2 on day 1 every 3 weeks. Results. All regimens shows high efficacy: objective responses in arm A obtained 96,9%, in arm В - 100%, in arm C - 100%. Median overall survival (OS) and progression free survival (PFS) in all arms not obtained. PFS at 1 year was significantly improved in arm A and В versus arm C: IIIb stage (arm A vs arm C, p=0,036; arm В vs arm C, p=0,005), pelvic lymph node metastases (arm В vs arm C, p=0,013), low-differentiation tumors (arm В vs arm C, p=0,013). 1-year OS did not shows improvement. Toxicity of all three regimens was tolerable. Conclusions. Our regimens showed high efficacy and tolerable toxicity. Significantly improvement in 1-year recurrence rate in poor-prognostic group of patients obtained encouraging results. Pending of medians OS and PFS allows to make the final conclusion about the benefits of combination chemoradiation therapy with adjuvant chemotherapy in LACC.

Development of first-line cytostatic therapy in ovarian cancer is slow, and as a result, the main research aim today is to study the biology of the disease. Angiogenesis is one of the main factors of the tumor microenvironment, resulting in growth and metastasis. As a result have been investigated the drugs inhibiting angiogenesis. The first drug being studied in phase III trial of the randomized studies was bevacizumab, which demonstrated the significant increase in both progression-free survival and survival in the high risk group. Other antiangiogenics such as pazopanib, nintenanib, also demonstrated high efficacy in patients with ovarian cancer.

Given the high rate of recurrence of epithelial ovarian cancer after radical treatment is necessary to improve the therapeutic approach to its treatment. New drug of marine origin trabectedin has shown high efficacy in monotherapy and in combination with different cytostatics in the treatment of platinum-sensitive recurrent of ovarian cancer. A randomized trial OVA-301 showed the greatest benefit of a combination of trabectedin with pegylated liposomal doxorubicin in the subgroup of patients with partially platinum-sensitive recurrent of ovarian cancer. Acceptable toxicity profile of the drug, presented mainly neutropenia and transient increase of transaminases, making it promising for further study.

Antitumor activity of trabectedin as a monotherapy in different solid tumors (soft tissue sarcoma, ovarian cancer, breast cancer, melanoma) contributed to research trabectedin-based drug combinations. Phase I trials were searching for optimal dose and schedule of administration trabectedin and trabectedin-based combinations. This review considers aspects of clinical applications and toxic profile of trabectedin alone and combinations, including a rare adverse event – rhabdomyolysis and data of own experience.

Последнее десятилетие характеризуется появлением и быстрым развитием нового направления лекарственной противоопухолевой терапии – таргетной терапии. Точкой приложения препаратов таргетной терапии являются определенные молекулярные структуры, мишени. Одной из таких мишеней являются рецепторы к эпидермальному фактору роста (EGFR), известные также как HER1 или ErbB1. EGFR относится к семейству ErbB-рецепторов. Информационные сигналы, возникающие при активации этих рецепторов, участвуют в механизмах пролиферации или дифференцировки клеток, стимулируют процесс клеточного деления. Рецептор эпидермального фактора роста состоит из экстрацеллюлярного домена, связывающегося с лигандом, гидрофобной липофильной трансмембранной части и внутриклеточного цитоплазматического домена, содержащего тирозинкиназный домен. Специфическими лигандами для EGFR являются эпидермальный фактор роста (EGF) и трансформирующий фактор роста (TGF)-α. Их связывание с экстрацеллюлярным доменом приводит к димеризации рецепторов. При этом могут образовываться как гомодимеры с другими EGFR, так и гетеродимеры с другими представителями семейства Erb, например с HER2, 3, 4. Димеризация стимулирует аутофосфорилирование тирозинкиназного домена, что в свою очередь активирует внутриклеточные каскады ферментативных реакций, передающих сигнал в ядро клетки, включая Ras-MAPK- и PI-3K-Akt пути.Гиперэкспрессия рецепторов эпидермального фактора роста обнаружена во многих злокачественных опухолях человека, включая рак толстой кишки, области головы и шеи, рак легкого, шейки матки, молочной железы, желудка, а также глиобластому, рак мочевого пузыря, яичников.Показано, что гиперэкспрессия EGFR в опухоли коррелирует с плохим клиническим прогнозом, стимулируя быстрый рост, размножение, а также дедифференцировку опухолевых клеток, блокируя апоптоз. Ферментативные реакции, участвующие во внутриклеточной передаче сигнала от EGFR, в частности PI-3K-Akt-путь, стимулируют также выработку фактора роста эндотелия сосудов, что приводит к активному неоангиогенезу и способствует быстрому метастазированию опухоли.Цетуксимаб (Эрбитукс) является моноклональным антителом IgG1, которое связывается с экстрацеллюлярным доменом EGFR, блокируя таким образом лигандиндуцированное фосфорилирование тирозинкиназного домена и активацию внутриклеточных путей передачи сигнала. Препарат обладает высокой специфичностью, его аффинитет к EGFR в 10 раз превышает аффинитет естественных лигандов EGF и TGF-α. Связывание Цетуксимаба с EGFR приводит также к димеризации рецептора с последующим эндоцитозом и внутриклеточной деградацией антитело-рецепторного комплекса. За счет этого механизма происходит снижение плотности EGFR на поверхности клетки.Как моноклональное антитело класса IgG1 Цетуксимаб способен активизировать NK-клетки и другие иммунные эффекторы, вызывающие лизис опухолевых клеток.

В последние 10 лет в онкологии появилось новое направление – таргетная терапия, которая постепенно вводится в стандарты лечения некоторых злокачественных новообразований. Для разработки таргетных препаратов используется научно обоснованный подход с проведением клинических исследований при определенном ограниченном круге опухолей, в которых высока частота экспрессии молекулярных мишеней для конкретного таргетного препарата. Одной из таких мишеней стали рецепторы к эпидермальному фактору роста (EGFR), ответственные за процесс передачи стимулирующего сигнала к ядру опухолевой клетки и, соответственно, к запуску активного деления клетки. Согласно ранее проведенным исследованиям гиперэкспрессия EGFR в опухоли сочетается с высоким риском развития метастазов, формированием резистентности к химио - и эндокринотерапии, снижением как безрецидивной, так и общей выживаемости [1]. Высокая экспрессия EGFR наблюдается при раке толстой кишки, головы и шеи, немелкоклеточном раке легкого, раке поджелудочной железы и раке шейки матки. При метастатическом раке толстой кишки у 82% пациентов обнаружена гиперэкспрессия EGFR-рецепторов [2]. К препаратам, блокирующим EGFR-сигнальный путь, относятся препараты, которые взаимодействуют с экстрацеллюлярным доменом рецептора, такие как Цетуксимаб, Матузумаб, Панитумумаб, и представляют собой моноклональные антитела (МАб), и малые молекулы, блокирующие процесс фосфорилирования тирозинкиназного (внутриклеточного) домена, – Гефитиниб и Эрлотиниб.В преклинических исследованиях Цетуксимаб показал высокую противоопухолевую активность и продемонстрировал синергизм в комбинации с химиотерапией, особенно с Иринотеканом, Цисплатином и лучевой терапией. На ксенографтных клетках НТ 29 и DLD1 опухоли толстой кишки комбинация Цетуксимаба с Иринотеканом тормозила рост опухоли намного больше, чем каждый препарат в монорежиме (p=0,05), и Цетуксимаб вызывал гибель опухолевых клеток, которые были резистентны к Иринотекану

Доцетаксел (таксотер) является представителем группы новых лекарственных средств - таксанов, обладающих оригинальным механизмом действия и оказавшихся высокоэффективными при многих злокачественных опухолях.В данной работе представлены результаты применения таксотера у больных с различными солидными опухолями, лечившихся в отделении химиотерапии РОНЦ им. Н.Н.Блохина РАМН с 1995 по 2001 г. За этот период лечение таксотером (монотерапия и комбинации) получили 216 больных с различными солидными опухолями, которым проведено 2110 курсов химиотерапии.Опыт нашего отделения подтверждает многочисленные результаты проведенных в различных странах исследований о том, что таксотер является препаратом с широким спектром противоопухолевой активности и может использоваться для лечения больных с разнообразными солидными опухолями.

Cervical cancer takes second place in morbidity and third place in mortality from gynecological cancer. Advanced stages among newly diagnosed cases is still large. The "gold standard" of treatment for locally advanced cervical cancer is chemoradiotherapy with cisplatin that results in a lower risk of death. Improvement of radiotherapy methods allowed to bring optimal dose to the primary tumor with the inclusion of regional metastasis areas with less risk of damage to surrounding healthy tissue and organs. The search for alternative combinations of cytostatics, modes of drug administration, adjuvant chemotherapy after chemoradiotherapy showed an increase in survival of patients with locally advanced cervical cancer.

Given the high rate of recurrence of ovarian cancer, the search for new therapeutic strategies are topical issue. According to various studies the effectiveness of drug treatment relapse depends on the platinum-free interval, increasing in proportion to its duration. If therapy is platinum-resistant recurrent ovarian cancer is a standard approach, the treatment of platinum-sensitive recurrent algorithm is not fully defined. Comparison of platinum and non-platinum combinations revealed the advantage of combined platinum- treatment for patients with platinum-free interval of more than 6 months without an increase in life expectancy. Non-platinum combination of trabected in with pegylated liposomal doxorubicin has shown comparable efficacy with an advantage in overall survival in patients with platinum-free interval of 6-12 months. A platinum-free interval prolongation by the use of non-platinum mode increases the efficiency of subsequent platinum-based therapy, increasing the life expectancy of patients. Currently under study molecular markers and prognostic factors allowing to define a group of patients who have the greatest benefit from the use trabectedin with pegylated liposomal doxorubicin as second-line chemotherapy.