Key concepts in glioblastoma therapy

Abstract

Glioblastoma is the most common form of primary brain cancer and remains one of the most aggressive forms of human cancer. Current standard of care involves maximal surgical resection followed by concurrent therapy with radiation and the DNA alkylating agent temozolomide. Despite this aggressive regimen, the median survival remains approximately 14 months. Meaningful strategies for therapeutic intervention are desperately needed. Development of such strategies will require an understanding of the therapeutic concepts that have evolved over the past three decades. This article reviews the key principles that drive the formulation of therapeutic strategies in glioblastoma. Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed.

Conversion of a Gemistocytic Astrocytoma to a Fibrillary Astrocytoma after Temozolomide and Radiation Therapy

“…Over the past two decades, conceptualization of astrocytomas has evolved from a collection of relatively homogenous cells to the recognition of distinct sub-populations of tumor cells to that of a complex organ, with constant interactions between tumor cells [3][4]. Pre-clinical data suggest that these differing sub-populations of cells exhibit distinct response to chemotherapy and radiation therapy [5][6].…”

“…For instance, recent studies suggest that malignant gliomas harbor subpopulations of "stem" like cells capable of differentiating into distinct cell fates [3,9]. Moreover, the process of dedifferentiation and differentiation appear highly dynamic [9][10][11].…”

FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells

“…Previous research has already implicated a complicated molecular network of signaling pathways in mediating the malignance of glioma. Monotherapy targeting 1 gene or signaling pathway usually leads to other compensative oncogenic activation, thus causing therapeutic resistance 2. Hence, exploring such therapeutic targets that are capable of regulating multiple molecules or signaling pathways in gliomagenesis and TMZ resistance will be beneficial for improvement of glioma treatment.…”

Molecular Physiology of G-CIMP+ Glioblastomas: Therapeutic Implications

“…Cancers previously thought to be single clinical entities are now stratified based on these molecular physiologies [2]. As an example, glioblastoma, the most common form of primary adult brain cancer [3], is now recognized as an umbrella term that encapsulates a spectrum of subtypes that are defined by shared molecular physiologies [4].…”