Genetic and therapeutic landscapes in cohort of pancreatic adenocarcinomas: next-generation sequencing and machine learning for full tumor exome analysis.

About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

[Regulatory role and anticarcinogenic properties of certain vitamins' active derivatives and vitamin-like substances].

Vitamins are low-molecular compounds consisting of an essential part of the human diet. After entering the human organism vitamins or their precursors can undergo chemical modification, changing their biological properties and regulatory activity. For many decades, vitamins were considered mainly as precursors of enzyme cofactors, and hypovitaminosis was interpreted as a deficiency of a particular metabolite resulting from enzyme's insufficient activity. However, with the development of molecular biology techniques and breakthrough in understanding of gene expression regulation and cell signaling mechanisms, as well as in molecular mechanisms of diseases associated with impaired functions, it became clear that there are significantly more active forms of vitamins, and their functions in the human body are more diverse than it had been suggested previously. The purpose of this review was to consider vitamins' and vitamins' derivatives regulatory and anti-tumor role and their potential for clinical application as main or adjuvant drugs for malignant neoplasms treatment. Material and methods. The present review is based on the results of literature analysis conducted in the Scopus, PubMed, Science Direct databases for the keywords «vitamin A AND cancer¼, «retinoids AND cancer¼, «vitamin D AND cancer¼, «vitamins AND cancer¼, «vitamins AND cancer¼. The search depth was 6 years (2016-2021). Results. Active forms of hydrophilic and lipophilic vitamins are key participants in the processes of chromatin remodeling, genome stability maintaining, covalent modification of proteins, including signaling and regulatory ones, and also act as chemical messengers themselves. Therefore, vitamin deficiency is associated with autoimmune and chronic diseases such as cancer, atherosclerosis, diabetes mellitus, etc. This review considers the regulatory role of active forms of vitamins, their derivatives and vitamin-like substances as well as their involvement in the process of carcinogenesis. Conclusions. Modern studies confirm the high therapeutic potential of vitamins: the use of pharmacological doses of vitamins or their derivatives may help to prevent or fight non-communicable diseases, including cancer.

Challenges Faced by Clinicians in the Personalized Treatment Planning: A Literature Review and the First Results of the Russian National Cancer Program.

Advances in cancer molecular profiling have enabled the development of more effective approaches to the diagnosis and personalized treatment of tumors. However, treatment planning has become more labor intensive, requiring hours or even days of clinician effort to optimize an individual patient case in a trial-and-error manner. Lessons learned from the world cancer programs provide insights into ways to develop approaches for the treatment strategy definition which can be introduced into clinical practice. This article highlights the variety of breakthroughs in patients' cancer treatment and some challenges that this field faces now in Russia. In this report, we consider the key characteristics for planning an optimal clinical treatment regimen and which should be included in the algorithm of clinical decision support systems. We discuss the perspectives of implementing artificial intelligence-based systems in cancer treatment planning in Russia.