MIGLIORE ARTICOLO DEL MESE CON PRIMO AUTORE ITALIANO

“Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors”

Elisabetta Lazzarini, Domenico Alessandro Silvestris, Giuseppe Benvenuto, Daniela Osti, Luigi Fattore, Rosina Paterra, Gaetano Finocchiaro, Paolo Malatesta, Antonio Daga, Alberto L. Gallotti, Rossella Galli, Giuliana Pelicci, Anna Tesei, Martina Bedeschi, Roberto Pallini, Lorenza Pasqualini, Chiara Romualdi, Angela Gallo, Lucia Ricci-Vitiani, Stefano Indraccolo

J Neurooncol. 2023;163(1):47-59. DOI: 10.1007/s11060-023-04287-6

Selezionato dal lettore: Giovanni Di Mauro

MOTIVATION: Despite advances in treatment modalities, glioblastoma is still characterized by poor prognosis due to its inevitable recurrence. Nevertheless, genomic and transcriptomic analysis of malignant cancer cell lines is providing growing knowledge of novel therapeutic targets for incurable diseases, such as glioblastoma.

In this paper researchers from 6 centers, part of the major Italian oncology network, the Alliance Against Cancer (ACC), aimed to study the genomic and transcriptomic assets of patient-derived glioblastoma stem-like cells (GSCs) collected from 94 adult patients between 2017 and 2019, at first and second surgical treatment (diagnosis and relapse).

The study showed that among the top 50 mutated genes, there are driver genes implied in gliogenesis, glial cell differentiation, regulations of neural precursor cells proliferation, cells adhesion, and S-adenosylmethionine metabolic pathway, such as TP53 (mutated in 44% of GSCs lines), PTEN (36%), RB1 (16%), NF1 (16%), POLD1, PIK3CA, EGFR, and MSH6. Interestingly some genes turned out to be more frequently mutated at diagnosis (mismatch repair, cell cycle, p53 signaling, and methylation genes) than at the first relapse (when tyrosine kinase and ERK/MAPK pathways are mainly involved). The great sample size considered in this study permitted to study rare genetic alterations previously missed, this is noteworthy because future studies may validate the therapeutic activity of specific inhibitors acting on the above-mentioned pathways. For example, a subset of GSCs with pV600E BRAF mutation was effectively tested in vitro with dabrafenib, a BRAF inhibitor, as proof-of-concept validation of a therapeutic target uncovered by this genomic profiling.

The meticulous design and the remarkable sample size used in this study allowed the clear representation of the genomic asset of glioblastoma stem-like cells, opening interesting scenarios about the discovery of novel therapeutic targets.

The is the major, with the aim of developing recommendations for cancer diagnosis and treatment and improving the quality of care.

MIGLIORE ARTICOLO IN ASSOLUTO

“Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis”

Ortega MC, Lebrón-Galán R, Machín-Díaz I, Naughton M, Pérez-Molina I, García-Arocha J, Garcia-Dominguez JM, Goicoechea-Briceño H, Vila-Del Sol V, Quintanero-Casero V, García-Montero R, Galán V, Calahorra L, Camacho-Toledano C, Martínez-Ginés ML, Fitzgerald DC, Clemente D.

Acta Neuropathol. 2023 May 27. doi: 10.1007/s00401-023-02593-x. Epub ahead of print. PMID: 37243699.

Selezionato dal lettore: Alessandro Furia

MOTIVATION: I propose this article due to the novelty of the research topic, being the first study to assess the presence of myeloid-derived suppressor cell-like cells (M-MDSCs) in actual human MS patients.

In this work, M-MDSCs were associated with MS lesions and appear to correlate with disease severity in primary progressive MS patients.

A significant number of patients post mortem were included, allowing for reliability of the results.

Data are well-presented and the article allows non-neuropathologists to understand the results and apply them to clinical practice.

The study is highly original as it assesses the correlation of M-MDSCs with clinical characteristics of MS in humans. The findings of this study are quite relevant, as reduction of M-MDSCs is suggested to be a possible biomarker of disease severity and activity, also being strongly related to past or future clinical course of the disease. In such a case, M-MDSC supplementation might be a potential new line of treatment.