new target has been identified in the battle against medulloblastoma
, one of the most aggressive pediatric brain tumors.
The authors of the pioneering study were researchers from the Department of Molecular Medicine of the Sapienza University of Rome, coordinated by Lucia Di Marcotullio, who identified
the role of the SALL4 protein and its inhibition in the treatment
A peculiarity of the research is the
possible use of thalidomide
- a drug sadly known in history for its highly toxic effects on the fetus - which however has shown a new face in the field of anti-tumor therapies.
It is currently used in the treatment of multiple myeloma and
ongoing clinical studies are evaluating its possible effectiveness for the treatment of brain tumors, including medulloblastoma
The study - reports a note - has therefore made it possible to identify for the first time the SALL4 protein as an important regulator of the Hedgehog signaling pathway, essential for embryonic development.
The research team also clarified that the abnormal accumulation of the protein interferes with this signaling pathway, causing its activation and consequent tumor growth.
Some research data have therefore suggested the use of thalidomide to induce the degradation of SALL4
in tumors that overexpress it.
The inhibition of SALL4 was in fact found to be effective both in blocking the growth of tumor cells and in counteracting the stem counterpart of the tumor, responsible for relapses and the failure of current therapies.
"To provide data to support the use of drugs that induce the degradation of SALL4 in the treatment of this pediatric tumor we employed a multidisciplinary approach, combining molecular biology techniques, gene expression analysis, protein-protein interaction studies and preclinical experiments with laboratory mice with medulloblastoma", comments Lucia Di Marcotullio together with researchers Ludovica Lospinoso Severini, who received an Airc scholarship, and colleagues Elena Loricchio and Shirin Navacci, authors of the study published in '
Cell Death & Differentiation
The research took place mainly at the Department of Molecular Medicine at Sapienza University, in collaboration with the Curie d'Orsay Institute, in France, and the Bambino Gesù pediatric hospital in Rome