Oncology of the beginning of XXI century: elements of individualized cancer treatment
Background. Early chemotherapy (ChT) was extremely toxic and dangerous. The paradigm has changed in the late ХХ century and the beginning of ХХІ century, when the first target drug imatinib was created and the scientists managed to decode a human genome. The main achievements of the postgenome era of cancer treatment include the molecular neoplasm classifications and the revealing of intertumoral heterogeneity. It was proven that the patients’ survival depends not only on the TNM stage, but also on the molecular subtype of the tumor.
Objective. To reveal the backgrounds of personalized cancer treatment.
Materials and methods. Analysis of the literature data on this topic.
Results and discussion. Targeted cancer treatment needs thorough diagnostics with the estimation of all tumor characteristic. According to their clinical value, modern oncomarkers can be divided into prognostic, surrogate and pharmacodynamical and can be assessed in tissues, blood, urine and other biological liquids or exhaled air. Analysis of cancer tissues now includes the assessment of genome, transcriptome, proteome, metabolome, lipidome, epigenome, microbiome, etc. Technologies of DNA sequencing are also developing: new generation methods allow to read billions of short DNA molecules simultaneously. According to the experts’ prognosis, in 2025 the complete genome sequencing will cost only 400 USD. New generation sequencing (NGS) has such possibilities as a complete metagenome sequencing, RNA sequencing, analysis of DNA-protein interactions, bisulfite sequencing and its modifications, target sequencing (exome, mitochondrial, amplicon sequencing). Advantages of NGS include high sensitivity and specificity, possibility of multiplexing, wide spectrum and high speed of mutations assessment, whereas its disadvantages include the need in an expensive equipment and high-quality calculations. Modern individual genome therapy of cancer can also be called personalized medicine, prognostic medicine, integrative medicine, pharmacogenomics medicine. In general, it meets the principles of Leroy Hood. According to his 4Р rule, the healthcare must be Рredictive, Preventive, Personalized and Participatory. Nowadays there is a new trend in the oncological science, which anticipates creating of the avatars of human tumors in genetically modified mice or Zebrafish (Danio rerio). It allows to cultivate tumor cells, taken from an individual patient, in a new organism, and to study their reaction to the various kinds of treatment. Personalization of treatment also cover the drug compounding, that is, creation of an individual pharmacological product taking into account the individual characteristics of each patients. Domestic compounding center “Khemoteka” provides personification of patients’ treatment and excludes the possible causes of the decrease of cytostatic dose during ChT. The prescription is made online, and individually created ready-to-use drug is delivered to the hospital.
Conclusions. 1. Accurate classification and the exact assessment of molecular and genetic characteristics of tumor is a background of the optimal treatment of cancer. 2. NGS allows to reveal a wide spectrum of mutations very fast. 3. Drug compounding is an important part of personalized cancer therapy.
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