Non-invasive methods of molecular diagnosis, clinical monitoring and approaches to the personalized therapy of diffuse midline glioma

Abstract

The purpose of the study was to summarize and analyze modern data about non-invasive methods of molecular diagnosis and approaches to the personalized therapy of diffuse midline glioma (DMG). Material and Methods. The search and analysis of publications was carried out using Google Scholar, Pubmed, Elsevier, Web of Science, Elibrary systems. The review includes publications published from 2011 to 2022. Of the 102 articles found, 59 were used to write the review. Results. In this review, we discuss the spectrum of somatic driver mutations present in DMG tumor cells and their relationship with the sensitivity of tumor cells to certain types of therapy - a pharmacogenetic approach to the selection of individual treatments (targeted therapy). We provide examples of new methods of targeted therapy for DMG, which are currently at the stage of preclinical laboratory development. Also, we discuss examples of the use of 3D cell cultures for the development of targeted therapies, including the use of perfusion systems. The review describes the methods of analysis of liquid biopsy, which allow the detection of tumor-specific biomarkers in the non-invasive diagnosis of DMG, including a number of methods that have not yet been tested in the clinic. The following is a list of tumor-specific biomarkers for diagnosing, monitoring, and selecting targeted therapy for DMG. Finally, we discuss the possibility of implementing these methods in the clinic and present the results of several clinical trials. Conclusion. In oncology, new methods of molecular genetics, such as analysis of liquid biopsy, allow diagnosis and monitoring of treatment in cases where classical methods that require tissue sampling are not applicable (for example, the analysis of genetically heterogeneous tumors and tumors of surgically inaccessible localization). These tumors include DMG, a primary brain tumor most common in children. The available data confirm the relevance of the search for new specific tumor biomarkers, as well as targets for targeted therapy of the paediatric-type diffuse gliomas.

Keywords

• non-invasive diagnostics
• tumors of the central nervous system
• diffuse brainstem gliomas
• molecular genetic markers
• h3k27m
• digital droplet pcr
• liquid biopsy
• ex-vivo 3d cell cultures
• 3d cell models
• biobanking