M. A. Revkova

The PI3K / AKT / mTOR signaling pathway plays a key role in regulating cell growth, metabolism, and survival and is one of the most frequently activated pathways in breast cancer. Mutations in the PIK3CA gene, which encodes the p110α catalytic subunit of PI3K, are detected in approximately 40 % of patients with hormone receptor — positive HER2-negative breast cancer and are most commonly located in exons 9 and 20. These mutations lead to constitutive activation of the PI3K / AKT / mTOR signaling pathway, promoting tumor cell growth, disease progression, and resistance to endocrine therapy. The presence of PIK3CA mutations is associated with a poorer prognosis, reduced relapse-free and overall survival, and a weaker response to chemotherapy in patients with metastatic breast cancer. In recent years, targeted PI3K and AKT inhibitors, such as alpelisib, inavolisib, and capivasertib, have been developed, and their use has demonstrated significant improvements in progression-free survival among patients with PIK3CA mutations. Modern molecular diagnostic methods, including polymerase chain reaction and next-generation sequencing (NGS), provide high accuracy in detecting these mutations, enabling personalized therapy and improving treatment effectiveness. Thus, PIK3CA mutations and activation of the PI3K / AKT / mTOR signaling pathway play a key role in the pathogenesis and treatment of breast cancer, and further investigation of these mechanisms, together with the implementation of comprehensive molecular analysis, is essential for optimizing anticancer therapy. Literature search methods. The search and selection of scientific literature on the PI3K / AKT / mTOR signaling pathway and PIK3CA gene mutations in breast cancer was conducted using international and national bibliographic databases, including Scopus, Web of Science, PubMed, and the Russian scientific electronic library eLIBRARY. RU. Additionally, materials from official resources, including ClinicalTrials. gov and the U. S. Food and Drug Administration, were used to obtain up-to-date information on clinical trials and drug approvals.

Inherited mutations in the BRCA1/BRCA2 genes significantly increase the risk of breast and ovarian cancer in women of reproductive age, posing a clinical and socioeconomic challenge due to loss of fertility during cancer treatment and preventive interventions. The expansion of genetic testing programs is shifting the focus to proactive management of reproductive potential, requiring the integration of oncology, reproductive medicine, and medical genetics. The novelty of this review lies in its comprehensive synthesis of data on the impact of treatment and prevention of BRCA-associated cancer on fertility and a critical assessment of the effectiveness of fertility preservation strategies. Purpose of the study . To summarize and analyze current advances, clinical guidelines, and unresolved issues related to preserving reproductive function in women carrying BRCA1/BRCA2 mutations. Materials and methods . A systematic search of PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science was performed, along with an analysis of international guidelines (ESHRE (European Society of Human Reproduction and Embryology), ASCO (American Society of Clinical Oncology), ASRM (American Society for Reproductive Medicine), NCCN (National Comprehensive Cancer Network), ESMO (European Society for Medical Oncology)). Keywords: “BRCA1,” “BRCA2,” “fertility preservation,” “oocyte cryopreservation,” “embryo cryopreservation,” “ovarian tissue cryopreservation,” “PGT-M,” “PARP inhibitors,” and “chemotherapy gonadotoxicity.”, in the period of 2005–2025. Studies with incomplete data, duplicates, reviews of low methodological quality, and case series with fewer than 10 observations were excluded. Priority was given to meta-analyses, RCTs, large cohorts, and consensus reports. Results. The included studies included cancer patients before and after treatment, BRCA carriers with and without prophylactic strategies, and IVF/ICSI cohorts with cryopreservation. Alkylating agents and taxanes have been shown to increase the risk of premature ovarian failure, while GnRH agonists partially reduce the risk of ovarian toxicity. The efficacy of oocyte and embryo cryopreservation in BRCA-positive women is comparable to the population-­based efficacy with optimized stimulation (GnRH antagonists, letrozole-­containing protocols). Ovarian tissue cryopreservation is applicable in urgently needed patients but requires oncoprotective assessment. PGT-M ensures the selection of mutation-free embryos. Multidisciplinary pathways improve the timelines of referrals and the completion rate of fertility preservation programs Conclusion. Early identification of BRCA-positive women and the integration of a gynecologic oncologist, reproductive specialist, and geneticist enable personalized strategy selection: gamete/embryo cryopreservation, ovarian tissue, pharmacoprotection, and PGT-M. Standardized stimulation protocols and therapy timing, long-term safety and fertility data, and economic access models are needed. Improvements in biotechnology and patient pathways improve reproductive outcomes and quality of life.

PIK3CA mutations represent one of the most frequent driver events in malignant neoplasms, particularly in hormone-dependent breast cancer. Activation of the PI3K/AKT/mTOR pathway promotes tumor growth, drug resistance, and poor prognosis. Objective. To assess the frequency and spectrum of clinically significant mutations in the PIK3CA gene in various types of malignant neoplasms in patients from a Russian cohort. Material and methods. The study included sequencing data from 1.556 tumor samples (1.452 patients) that underwent molecular genetic testing at the National Medical Research Radiology Center of the Ministry of Health of the Russian Federation between 2022 and 2025. Targeted panels and whole-exome sequencing with a coverage depth of 200—1000× were used. Analysis was performed according to GATK Best Practices; annotation was conducted using VEP and OpenCaravat; statistical analysis was carried out in Python. Results. PIK3CA mutations were identified in 12.1% of all samples, with a frequency of 26.8% in breast cancer and 5.1% in other tumor types (p<10–6). The most common variants were H1047R (29%), E545K (19.9%), and E542K (9.9%). Co-mutations were most frequently observed with TP53 (38.8%) and less often with KRAS and PTEN. Conclusion. The PIK3CA mutation spectrum in the Russian cohort generally corresponds to global data and confirms the significance of the PI3K/AKT/mTOR pathway as a key target for precision therapy, especially in hormone-dependent tumors.

Malignant neoplasms remain one of the leading causes of death worldwide, continuously driving the development and active implementation of new innovative treatments into clinical practice. This article provides a comprehensive review of the current status and prospects for the application of mRNA technologies in oncology, analyzing global clinical trial experience, the mechanism of action of therapeutic mRNA cancer vaccines, manufacturing processes, and the regulatory framework for the introduction of individual biotechnologically modified drugs (iBTMD) in the Russian Federation.