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Basic premises: searching for new targets and strategies in diffuse gliomas

Abstract

Purpose

Diffuse gliomas represent the most frequent primary brain tumours in adults. In the last years, landmark studies led to tremendous advances in terms of the knowledge of the molecular bases of gliomagenesis. This resulted in a paradigm shift in their classification. Regrettably, such advances have not yet corresponded to comparable improvements in terms of patient outcome. New approaches and therapies are compellingly needed.

Method

We performed a literature review for articles on the topic in PubMed, Google Scholar, and Web of Science until January 2022. Search keywords included “glioma”, “glioblastoma”, “tumour microenvironment”, “immunotherapy”, “targeted therapy”, and “radiomics”.

Result

This review will present the novelties in the classification system of diffuse gliomas, focusing on its molecular determinants with major prognostic and therapeutic significance. We will recapitulate progresses regarding potentially or already actionable alterations and proposed targeted therapeutical strategies. Another section will cover the glioma microenvironment and its exploitable therapeutical potential. Established and emerging aspects of immunotherapy in this field will be discussed. Lastly, we will discuss the potential of medical imaging in the field. Particularly, we will introduce the concepts of radiomics, radiogenomics, and the applications of artificial intelligence to them.

Conclusion

Diffuse gliomas show resistance to several molecularly targeted therapies and immunotherapies effective in other solid cancers. Glioma heterogeneity and the immunologically “cold” microenvironment have been invoked as possible reasons. Nonetheless, novel approaches can be beneficial in specific populations of glioma patients. In this complex interplay, medical imaging can reliably generate data at “-omics” level with predictive, theranostic, and/or prognostic purposes.

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Adapted from Brennan et al., Cell 2013 [43]

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Acknowledgements

G.S, N.V., A.L.D.S., and A.P. are grateful to Premio Carla Russo and Palummo family for their support. A.P. receives support from “Fondation pour la Recherche Médicale” (Grant FDM202106013569) independently from this work.

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Correspondence to Alberto Picca.

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Sansone, G., Vivori, N., Vivori, C. et al. Basic premises: searching for new targets and strategies in diffuse gliomas. Clin Transl Imaging 10, 517–534 (2022). https://doi.org/10.1007/s40336-022-00507-7

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Keywords

  • Diffuse gliomas
  • Glioblastoma
  • Targeted therapies
  • Brain tumours
  • Immunotherapy
  • Glioma microenvironment
  • Radiomics