Materials of the 6th All-Russian Conference on Molecular Oncology

Materials of the 6th All-Russian Conference on Molecular Oncology.Moscow, 21–23 December 2021

The molecular tumor board: a tool for the governance of precision oncology in the real world

Clinical oncology is going through a period of profound change. Targeted therapy, and more recently immunotherapy, have revolutionized the natural history and outcomes of many solid tumors. Clinical oncology is now indissoluble from molecular oncology, a rapidly evolving field. This profound transformation is the rationale for molecular tumor board (MTB) implementation. MTBs represent a resource for the development of precision oncology and clinical practice implementation is a complex and important challenge for the future of clinical and molecular oncology. Economic sustainability of genomic tests, access to drugs or clinical trials according to the MTB recommendation, and expanded use of existing anticancer drugs are required for MTBs to become a useful tool for the governance of precision oncology in the real world. This is an ongoing process, with establishment of MTBs the first step. Continuing to work in collaboration with scientific societies, MTBs are poised to become a homogeneous and well-structured reality that can make the care pathway of the patient with cancer more efficient, with the ultimate goal to offer personalized therapy based on the most advanced scientific knowledge.

Galangin: A metabolite that suppresses anti-neoplastic activities through modulation of oncogenic targets

With the dramatic increase in cancer incidence all over the world in the last decades, studies on identifying novel efficient anti-cancer agents have been intensified. Historically, natural products have represented one of the most important sources of new lead compounds with a wide range of biological activities. In this article, the multifaceted anti-cancer action of propolis-derived flavonoid, galangin, is presented, discussing its antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, anti-angiogenic, and anti-metastatic effects in various cancer cells. In addition, co-effects with standard chemotherapeutic drugs as well as other natural compounds are also under discussion, besides highlighting modern nanotechnological advancements for overcoming the low bioavailability issue characteristic of galangin. Although further studies are needed for confirming the anti-cancer potential of galangin in vivo malignant systems, exploring this natural compound might open new perspectives in molecular oncology.

Linc01018 / hsa-mir-182-5p / ADH4 Axis Study on the Role and Mechanism in the Occurrence and Development of Liver Cancer

Background To construct the lncRNA-miRNA-mRNA axis based on the study of molecular oncology, to explore the role and mechanism of this axis in the occurrence and development of liver cancer, so as to provide a new channel for the treatment of liver cancer. Methods Using public online databases to establish lncRNA-miRNA-mRNA ceRNA regulation network, after which using QPCR and other experimental techniques to verify that this axis is established and the mechanism of participating in the development of liver cancer. Results It can be concluded from database mining that the expressions of hsa-miR-182-5p and ADH4 are negatively correlated in hepatocellular carcinoma, and LINC01018 is also negatively correlated hsa-miR-182-5p-ADH4, indicating that LINC01018, hsa-miR-182-5p and ADH4 are strongly correlated. Constitute the regulatory axis to participate in the occurrence and development tendency of tumors. LINC01018 regulates ADH4 to inhibit LIHC cell growth by inhibiting hsa-miR-182-5p, providing a feasible theoretical basis for the treatment of HCC.The regulatory axis may also regulate the occurrence and development tendency in liver cancer by adjusting the expression levels of key proteins and phosphorylation proteins in GO and KEGG signaling pathways. Conclusions In this study, it was found that LINC01018/hsa-miR-182-5p/ADH4 ceRNA regulatory axis exists in the human body, and this axis has the possibility of becoming an immune checkpoint inhibitor for liver cancer, which is regarded as a new entry point in the diagnosis and therapy of liver cancer.

Integrating molecular profiles into clinical frameworks through the Molecular Oncology Almanac to prospectively guide precision oncology

Tumor molecular profiling of single gene-variant (‘first-order’) genomic alterations informs potential therapeutic approaches. Interactions between such first-order events and global molecular features (for example, mutational signatures) are increasingly associated with clinical outcomes, but these ‘second-order’ alterations are not yet accounted for in clinical interpretation algorithms and knowledge bases. We introduce the Molecular Oncology Almanac (MOAlmanac), a paired clinical interpretation algorithm and knowledge base to enable integrative interpretation of multimodal genomic data for point-of-care decision making and translational-hypothesis generation. We benchmarked MOAlmanac to a first-order interpretation method across multiple retrospective cohorts and observed an increased number of clinical hypotheses from evaluation of molecular features and profile-to-cell line matchmaking. When applied to a prospective precision oncology trial cohort, MOAlmanac nominated a median of two therapies per patient and identified therapeutic strategies administered in 47% of patients. Overall, we present an open-source computational method for integrative clinical interpretation of individualized molecular profiles.

The effect of antioxidants in Ehrlich Ascites Cancer

A fundamental goal in molecular oncology is to unravel the underlying mechanisms which cause the cell transformation. In line with this approach, genome-wide functional screening approaches have revealed exciting insights into heterogeneous nature of cancer. Rapidly expanding horizons of research have unraveled myriad of pathways which play instrumental role in carcinogenesis and metastasis. Oxidative stress has also been reported to be significantly involved in cancer onset and progression. In line with this approach, oxidative stress modulating chemicals have always been sharply divided into antioxidants and oxidative stress-inducing agents. Conceptual and experimental advancements have enabled us to critically analyze full potential of these two different groups of chemicals in cancer chemoprevention. Different antioxidants are currently being analyzed in different phases of clinical trials. Although it has been reported in the literature that antioxidant supplements reduce tumor cells in some tumors or cause volume reduction in solid tumor sizes, there is no definite consensus. Therefore, an antioxidant supplement guideline based on more detailed clinical research and as a result of these is needed to achieve the best care for cancer patients and to avoid risky treatments for cancer patients.

Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss"

There has been an exponential growth in the field of molecular oncology and cutting-edge research has enabled us to develop a better understanding of therapeutically challenging nature of cancer. Based on the mechanistic insights garnered from decades of research, puzzling mysteries of multifaceted nature of cancer have been solved to a greater extent. Our rapidly evolving knowledge about deregulated oncogenic cell signaling pathways has allowed us to dissect different oncogenic transduction cascades which play critical role in cancer onset, progression and metastasis. Pharmacological targeting of deregulated pathways has attracted greater than ever attention in the recent years. Henceforth, discovery and identification of high-quality biologically active chemicals and products is gaining considerable momentum. There has been an explosion in the dimension of natural product research because of tremendous potential of chemopreventive and pharmaceutical significance of natural products. Schisandrin is mainly obtained from Schisandra chinensis. Schisandrin has been shown to be effective against different cancers because of its ability to inhibit/prevent cancer via modulation of different cell signaling pathways. Importantly, regulation of non-coding RNAs by schisandrin is an exciting area of research that still needs detailed and comprehensive research. However, we still have unresolved questions about pharmacological properties of schisandrin mainly in context of its regulatory role in TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways.