Clinical and pre-clinical utility of genomics in medulloblastoma.
Expert Rev Neurother
; 18(8): 633-647, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-30032687
ABSTRACT
INTRODUCTION:
Integrated genomics has significantly advanced our understanding of medulloblastoma heterogeneity. It is now clear that it actually comprises at least four distinct molecular subgroups termed Wnt/Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4 with stark clinical and biological differences. Areas covered This paper reviews advances in the classification and risk stratification of medulloblastoma, specifically integrating subgroup with clinical and cytogenetic risk factors, with a summary of the potential to lead to more precise therapies. Moreover, the current state of preclinical modeling is summarized with respect to their utility in generating new treatments and correlation with genomic discoveries. Opportunities and challenges in developing new treatment paradigms are summarized and discussed, specifically new therapies for very high-risk metastatic/MYC-amplified Group 3 and TP53-mutant SHH and reductions in therapy for lower risk groups. Expert commentary Survival across medulloblastoma has been stagnant for over 30 years, and new treatment paradigms are urgently required. Current therapy significantly over treats a high proportion of patients leaving them with lifelong side effects; while many patients still succumb to their disease. Applying biological advances could improve quality of life for a significant proportion of patients while offering new upfront approaches to the highest risk patients.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cerebellar Neoplasms
/
Genomics
/
Medulloblastoma
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspects:
Patient_preference
Limits:
Child
/
Humans
Language:
En
Journal:
Expert Rev Neurother
Journal subject:
NEUROLOGIA
/
TERAPEUTICA
Year:
2018
Document type:
Article
Affiliation country:
Canada