Molecular Characteristics and Personalized Treatment for Pediatric Brain Tumors

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Background

Pediatric brain tumors (PBTs) are the most common solid childhood cancers and the second most common form of childhood cancers, exceeded in incidence only by the leukemias, and have the highest mortality rate among all childhood cancers. These tumors are primarily treated with surgical resection, adjuvant with radiation or chemotherapy. However, radiation causes serious side-effects, and its use in young children is limited. Chemotherapy has been used as a first-line treatment to delay or replace radiotherapy in certain situations, such as critical tumor location, or relapsed tumors after surgery. Despite the advances and refinements in neurosurgical techniques, radiation, and chemotherapy, the outcome improvement for children with malignant brain tumors is still limited.

Most of the PBTs have recently been comprehensively profiled at genomic and epigenomic levels, which leads to the WHO classification update. PBTs with specific and unique molecular alterations are discovered and introduced. For example, the clinical and molecular distinctions between "pediatric-type" and "adult-type" diffuse gliomas are fully recognized and the division of the classification stands for a step forward in clearly separating these prognostically and biologically distinct groups of tumors, which may enable improved care for the pediatric patients. Meanwhile, molecularly targeted therapy is beginning to be incorporated into management and holds the promise of radically altering approaches and improving outcomes. Thus, current care for pediatric brain tumors is more molecularly based and personalized treatment. To this end, multi-disciplinary team co-operations from neurosurgeons, radiation oncologists, pediatric oncologists, radiologists, pathologists, neuro-rehabilitation therapists, and social psychologists are needed.

This Research Topic focuses on the progress of novel discoveries in PBT tumor biology, molecular and clinical diagnosis, and precision personalized treatments. We welcome studies about genomic and epigenomic characterizations, and potential therapeutic approaches for common pediatric brain tumors including low- and high-grade gliomas, ependymomas, medulloblastomas, atypical teratoid/rhabdoid tumors, and other rare embryonal tumors, in various article types including Original Research, Perspectives, Reviews, Mini Reviews.

The contents covered in this Research Topic include but are not limited to the following subtopics:

- Genetic and epigenetic profiling of tumors that allows for further subgrouping of heterogeneous tumor groups with therapeutic and prognostic impacts.

- Identification of potential diagnostic, therapeutic targets, or prognostic markers for PBTs, with in vitro cell model, tumor specimen, or more accessible specimens such as blood and/or CSF (Liquid biopsy).

- The establishment of new genetically modified animal models, PDX models, and brain organoid models for pediatric brain tumors.

- Molecular characterization and mechanism studies of tumor initiation, progression, and/or recurrence.

- Novel progress and associated prospective effects on molecular diagnosis, classification, and treatment.

- Discussion on the role and the risk of aggressive neurosurgical "total" resections, and subsequent consequences.

- Investigation on optimal timing and strategies for delivering radiation therapy for PBTs (including some benign tumors, e.g., pilocytic astrocytomas), and discussion on protons versus photon radiation therapy and late effects.

- Novel effective post-chemotherapeutic regimens post neurosurgical resection with/without radiation and/or molecular target therapies.

- Progress on immunotherapy for PBTs using checkpoint inhibitors, tumor vaccines, and CAR T-cell.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: Pediatric brain tumors, Neoplasms, Molecular Classification, Diagnosis, Treatment

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