Title:Genetic Markers as Predictors for Response to Treatment and Possible
Therapeutic Targets in Medulloblastoma
Volume: 22
Issue: 5
Author(s): Perla-Lidia Pérez-Pineda, Rocío Ortiz-Butrón, Juan-Carlos Pérez-De Marcos, Laura M. Hernández-Regino, Marta-Margarita Zapata-Tarrés and Luz-María Torres-Espíndola*
Affiliation:
- Laboratory of Pharmacology, National Institute of Pediatrics, Mexico City, México
Keywords:
Medulloblastoma, sonic hedgehog, wingless, MYC, MYCN, therapy.
Abstract:
Background: Medulloblastomas (MB) are the most common malignant brain tumors in the
pediatric age. In 2021, WHO categorized medulloblastomas into two groups: molecularly defined and
histologically defined medulloblastomas. Molecularly defined medulloblastomas are divided into WNTactivated
medulloblastoma, SHH-activated and TP53-wildtype medulloblastoma, SHH-activated, and
TP53-mutant and non-WNT/non-SHH medulloblastoma, which include Group 3 (MYC) and Group 4
(CDK6 and MYCN). In this paper, we will focus on molecularly defined medulloblastomas.
Objective: This paper aims to review the literature in order to describe the molecular structure of the
medulloblastoma groups and to emphasize the importance of genetic predictors in medulloblastoma
that can be used in clinical practice, either as a prognostic tool or as a therapeutic target in the future.
Results: Each molecular subtype of medulloblastoma presents a different prognosis, and the molecular
subtype with the best prognosis is medulloblastoma-activated WNT. It has even been observed that a
reduction in the intensity of the combined treatment does not modify the prognosis of the patients,
resulting in even fewer adverse effects due to the treatment. On the other hand, it was observed that the
subtypes with the worst prognosis are medulloblastomas with activated MYC and medulloblastomas with
activated SHH and mutated TP53, due to their high capacity to metastasize or to their radio-resistance.
However, a new target therapy has emerged that could help improve the prognosis in these patients.
Conclusion: The deeper knowledge of the molecular pathways involved in the appearance and
progression of medulloblastomas will allow us to offer a prognosis at the time of diagnosis and more
specific treatments through the development of the targeted therapy.
