TY - JOUR
T1 - Genetic Markers as Predictors for Response to Treatment and Possible Therapeutic Targets in Medulloblastoma
AU - Pérez-Pineda, Perla Lidia
AU - Ortiz-Butrón, Rocío
AU - Marcos, Juan Carlos Pérez De
AU - Hernández-Regino, Laura M.
AU - Zapata-Tarrés, Marta Margarita
AU - Torres-Espíndola, Luz María
N1 - Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023
Y1 - 2023
N2 - 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 WNT-activated 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.
AB - 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 WNT-activated 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.
KW - MYC
KW - MYCN
KW - Medulloblastoma
KW - sonic hedgehog
KW - therapy
KW - wingless
UR - http://www.scopus.com/inward/record.url?scp=85150225575&partnerID=8YFLogxK
U2 - 10.2174/1871527321666220509141030
DO - 10.2174/1871527321666220509141030
M3 - Artículo
C2 - 35579144
AN - SCOPUS:85150225575
SN - 1871-5273
VL - 22
SP - 634
EP - 642
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
IS - 5
ER -