№78. The most important events in Oncology in 2018
FUNDAMENTAL ONCOLOGY IN 2018: AN OVERVIEW OF THE MOST INTERESTING DISCOVERIESE.N. Imyanitov
This review is dedicated to the most interesting developments in the fundamental
oncology in 2018. Noted advances in immuno-oncology. It presents information
about new aspects of the pathogenesis of tumor growth. Promising approaches to
the development of innovative cancer treatments are discussed.
Keywords: fundamental oncology, immuno-oncology, abscopal response, systemic inflammation, arginine, mannose, liquid biopsy.
2018 NOBEL PRIZE IN PHYSIOLOGY OR MEDICINEF.V. Moiseenko, V.M. Moiseyenko
During more than one hundred years The Nobel Prize remains the recognition of
the major advance of great social and fundamental importance. 2018 Nobel Prize in
Physiology or Medicine was awarded for the discovery of cancer therapy by inhibition
of negative immune regulation. This article describes the history of the discovery and
its role for clinical oncology as far as the questions that should still be solved.
Keywords: cancer, treatment, immunotherapy, checkpoint inhibitors.
ARTIFICIAL INTELLIGENCE IN ONCOLOGY: A LOOK INTO THE FUTURESh.Kh. Gantsev, M.V. Frants.
The article contains a brief overview of the history of development and modern achievements of artificial intelligence, as well as the possibilities of its application to cancer prevention, diagnosis and treatment. The progress of machine learning associated with the development of deep neural networks technology is discussed. The achievements in the automatic recognition of medical images including digital micrographs and radiographs are pointed out. The possibilities of applying artificial intelligence to high-risk groups formation for screening programs are discussed. The problems of introducing artificial intelligence into practical oncology are considered, which are related to the need of clinical trials of medical technologies based on artificial intelligence and the need for large volumes of qualitative data for neural networks training.
Keywords: artificial intelligence, machine learning, neural networks, automatic recognition, medical imaging, cancer.
MOLECULAR-ORIENTED AND PRECISION CANCER THERAPY – THE PRESENT AND FUTURE ASPECTSD.B. Korman
Molecular-oriented cancer therapy implies the use of antitumor drugs made to
interact with preset molecular targets which play an important (key) role in the onset
and development of tumors. In accordance with this strategy the drug is prescribed to
a patient with an appropriate tumor containing a suitable target. Precision therapy
is based on the results of sequencing the patient’s tumor DNA. Thus the spectrum
of molecular targets in this particular tumor can be identified, and the drug can be
selected accordingly irrespective of a tumor type (tumor-type agnostic therapy). The
present-day state of molecular-oriented and precision therapy was analyzed, and the
prospects of its use for raising the efficacy of therapy in routine clinical practice were
Keywords: cancer, molecular-oriented drugs, precision therapy, sequencing DNA, tumor-associated mutations, tumor-type agnostic therapy.
THE METHYLATION STATUS ROLE OF FIVE 3p21.31 REGION GENES IN THE MOLECULAR SUBTIPS OF BREAST CANCER PATHOGENESISD.A. Ryabchikov, E.A. Filippova, I.V. Pronina, A.M. Burdenny, S.C. Lukina, T.P. Kazubskaya, I.K. Vorotnikov, I.A. Dudina, A.M. Kazakov, O.A. Talipov, V.I. Loginov, E.A. Braga, K.S. Titov
In the last decade it was shown that in a multistage process of tumor formation, the alterations of cellular genes can occur not only as a result of genetic events (point mutations, deletions, amplifications), but also as a result of epigenetic changes, including local DNA hypermethylation. For last period, for the identification of hypermethylated regions of DNA have been used methods, based on the differential methylation status of CpG islands in normal and tumor cells. Aim. The aim of this study is to assess the methylation status of the tumor-associated genes group RASSF1A, RHOA, GPX1, DAG1 and USP4 in various biological subtypes of breast cancer, and also to assess their connection with the clinical course of the disease. Methods. Methylation status analysis was performed on 174 paired samples of the tumor and the adjacent histologically unchanged tissue from the patients with breast cancer and 20 breast tissue samples from healthy women. Two independent methods were used: methylation specific PCR (for RASSF1A) and methyl sensitive restriction analysis (for RHOA, GPX1, DAG1 and USP4).
Results. A statistically significant higher frequency of methylation of the RASSF1A, GPX1 and DAG1 genes in the tumor was shown compared to that in the histologically normal tissue (p<0,00001, p=0,0327 and p=0,0374, respectively). An interesting fact is that in the group of patients without methylation of the RASSF1A genes, 5- and 10-year survival was 93,5%
and 85,5%, respectively, and with methylation it decreased to 80,3% and 65,3% (p=0,007), respectively.
Conclusion. Methylation of the genes RASSF1A, GPX1, DAG1 plays an important role in the pathogenesis of luminal breast cancer, changing the functional activity of these genes. Methylation of RASSF1A genes is associated with an adverse clinical outcome of breast cancer. Epigenetic changes of these genes in combination or separately can be included in the biomarker system, which could help in the diagnosis, prognosis of the disease, and especially in the development of individual tactics for the treatment of breast cancer.
Keywords: luminal and non-luminal breast cancer, gene methylation, promoter region, CpG-island.
EVOLUTION OF DRUG THERAPY FOR LUNG CANCER WITH EGFR INHIBITORS: NEW ASPECTSM.L. Stepanova, L.V. Khalicova, A.S. Zhabina, F.V. Moiseenko
One of the main events in the last 20 years in the treatment of NSCLC is the discovery in some patients of activating mutations of the epidermal growth factor receptor (EGFR). The use of tyrosine kinase inhibitors (TKI) significantly improved both the frequency of the objective response, the time to progression, and overall survival. When applying the 1st and 2nd generation EKFR TKI (gefitinib, erlotinib, afatinib) in patients with NSCLC associated with EGFR mutations, after 8–12 months, resistance to EGFR TKI therapy develops. Among the large number of identified molecular disorders that determine the loss of sensitivity of the tumor to therapy, the most frequent is the appearance of the T790M EGFR mutation. The first targeted drug that was approved for clinical use in patients with NSCLC who had previously received EGFR TKI was osimertinib, an irreversible third-generation EGFR tyrosine kinase inhibitor that binds to cysteine at 797 position of the EGFR tyrosine kinase. One of the key aspects is that only 73–77% of patients can receive treatment for EGFR+ NSCLC in the second line, since some patients may die from the progression of the process against he background of first-line or second-generation TKI therapy or objective status not meeting the criteria for prescribing osimertinib. The review will also present the clinical cases of the use of osimertinib, both in the first and in the second line of drug treatment in EGFR NSCLC.
Keywords: non-small cell lung cancer, epidermal growth factor receptor, targeted therapy, osimertinib.
IMPLEMENTATION OF AN INNOVATIVE APPROACH IN MEDICINE ON THE EXAMPLE OF THE INTELLECTUAL SYSTEM OF LUNG CANCER DIAGNOSIS «DOCTOR AIZIMOV»A.A. Meldo, L.V. Utkin, V.M. Moiseyenko, T.N. Trofimova, A.A. Lukashin, M.A. Ryabinin
The article describes the computer aided diagnosis (CAD) system of lung cancer Doctor AIzimov, which has the features of different types of innovation (product, process, marketing, organizational). This fact should be taken into account in implementation of the CAD system. We present the scheme of implementation of the system in medical practice based on a network platform, which is aimed at improving the quality of medical care, focused on needs of patients and does not contradict the classic design of the diagnostic process. This scheme is a cause and a result of the continuous improvement of the radiology department.
Keywords: diagnostic system, lung cancer, Doctor AIzimov, quality of medical care, patient, radiation diagnosis.
PROGNOSTIC SIGNIFICANCE OF STEM CELLS TUMORS AND ALK EXPRESSION IN PATIENTS WITH PRIMARY SKINMELANOMAK.S. Titov, M.A. Baryshnikova, A.M. Kazakov, D.A. Khochenkov, E.P. Larionova, D.A. Ryabchikov
Melanoma is the most malignant and aggressive skin tumor. Cancer stem cells (CSCs) can be one of the causes of low sensitivity of skin melanoma to chemotherapy, a short therapeutic effect and the development of resistance to targeted therapy, as well as the lack of effect of immunotherapy with inhibitors of control points of the immune system. Great importance is attached to the role of CSCs in the recurrence of the disease. CSCs is also susceptible to various mutations, but often it does not identify driver mutations characteristic of melanoma (BRAF, MEK, RAS, etc.), this phenomenon requires the search for new targets for targeted therapy, one of which can be Anaplastic lymphoma kinase (ALK).
Keywords: tumor stem cell, ABCB5, CD133, ALK, lymphoid infiltration, 2-year survival.
SCHWANNOMA OF THE POSTERIOR MEDIASTINUM (LITERATURE REVIEW AND RARE CLINICAL CASE)I.V. Mosin, O.V. Tikhonenko, A.A. Meldo, S.M. Nuraliev, V.M. Moiseyenko
This article presents a literature review on posterior mediastinal schwannoma. Morphological features, diagnostics and principles of treatment of posterior mediastinal schwannoma are stated.
A rare clinical case is presented-schwannoma of the posterior mediastinum with distribution into the retroperitoneal space through the triangle of the diaphragm Bochdalek. The difficulty of diagnosis of schwannoma is primarily due to the anatomical features of the retroperitoneal space, the vastness and elasticity of which allows the tumor for a long time not to manifest itself clinically, and at the time of detection the tumor can reach significant sizes. The correct recognition of the tumor spread from the pleural cavity of the posterior mediastinum to the retroperitoneal space through the triangle
of the diaphragm Bochdalek made it possible to determine the optimal surgical approach and radically remove the giant
Keywords: posterior mediastinum, schwannoma, peripheral nerve sheath tumor, retroperitoneal spaces, Bochdalek triangle.