For years, the group led by Lucia Di Marcotullio has been conducting research in the field of oncology in the laboratories of Sapienza in Rome to understand molecular mechanisms and identify innovative therapeutic paths. Recently, the group has added a new line of work to better understand and treat medulloblastoma, one of the most aggressive paediatric brain tumours.

The study identified for the first time the SALL4 protein as an important regulator of the Hedgehog signalling pathway, which is essential for embryonic development.  Di Marcotullio and colleagues also clarified that abnormal accumulation of the protein interferes with this signalling pathway, causing its activation and subsequent tumour growth.

One of the most promising aspects of their results concerns data suggesting the use of thalidomide as a therapeutic strategy to induce SALL4 degradation in tumours that overexpress it. Indeed, SALL4 inhibition has been shown to be effective in blocking both tumour cell growth and the tumour stem cells responsible for relapse and failure of current therapies.

Thalidomide, known in history for its role as a drug with highly toxic effects on the foetus, has shown a new face in the field of cancer therapy. It is currently used to treat multiple myeloma. Ongoing clinical trials are investigating its potential efficacy in the treatment of brain tumours, including medulloblastoma, offering a promising and innovative perspective.

"To provide data to support the use of drugs that induce SALL4 degradation in the treatment of this paediatric tumour, we used a multidisciplinary approach, combining molecular biology techniques, gene expression analysis, protein-protein interaction studies and preclinical experiments with medulloblastoma laboratory mice" – says Lucia Di Marcotullio together with the researchers who conducted the study: Ludovica Lospinoso Severini, who received an AIRC scholarship, and her colleagues Elena Loricchio and Shirin Navacci. The research took place mainly at Sapienza's Department of Molecular Medicine in collaboration with the Curie d'Orsay Institute in France and the Bambino Gesu` Children's Hospital in Rome. The results have been published in the journal Cell Death & Differentiation.

"The transition from scientific research results to possible application in patients", says Di Marcotullio, "could be translated into a public benefit, the ultimate goal of tenacious work carried out between laboratory benches, patients to follow, cells and mice to look after, ideas to persevere, hypotheses to prove and, above all, dedication and perseverance. The researchers are grateful to the AIRC Foundation, which has supported cancer research in Italy for decades with valuable funding, and in particular for making the project possible and awarding a grant to Ludovica Lospinoso Severini, first author of the paper.

References: 

SALL4 is a CRL3^REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma - Ludovica Lospinoso Severini, Elena Loricchio, Shirin Navacci, Irene Basili, Romina Alfonsi, Flavia Bernardi, Marta Moretti, Marilisa Conenna, Antonino Cucinotta, Sonia Coni, Marialaura Petroni, Enrico De Smaele, Giuseppe Giannini, Marella Maroder, Gianluca Canettieri, Angela Mastronuzzi, Daniele Guardavaccaro, Olivier Ayrault, Paola Infante, Francesca Bufalieri & Lucia Di Marcotullio - Cell Death & Differentiation – Doi: https://doi.org/10.1038/s41418-023-01246-6

Further Information

Lucia Di Marcotullio
Department of Molecular Medicine
lucia.dimarcotullio@uniroma1.it