Current clinical management of patients with glioblastoma

Abstract

BackgroundGlioblastoma (GB) is the most aggressive primary brain tumor, historically resistant to treatment, and with overall fatal outcome.Recent findingsRecently, several molecular subgroups and rare genetic alterations have been described in GB. In this review article, we will describe the current clinical management of patients with GB in the United States, discuss selected next‐generation molecular‐targeted therapies in GB, and present ongoing clinical trials for patients with GB. This review is intended for clinical and preclinical researchers who conduct work on GB and would like to understand more about the current standard of treatment of GB patients, historical perspectives, current challenges, and ongoing and upcoming clinical trials.ConclusionsGB is an extremely complex disease, and despite recent progress and advanced therapeutic strategies, the overall patient's prognosis remains dismal. Innovative strategies and integrative ways of approach to disease are urgently needed.

A Drug Screening Pipeline Using 2D and 3D Patient-Derived In Vitro Models for Pre-Clinical Analysis of Therapy Response in Glioblastoma

“…In addition, while glioblastoma tumors are highly heterogeneous, it is likely that glioblastoma patients will be classified, based on their response to different treatments and metadata information, only into a small number of “responder” groups. For example, thus far only three tumor subtypes, four cancer stem cell transcriptional states and a few biomarker-based predictors of therapy response ( MGMT methylation and IDH1 mutation) have been described [ 37 ]. Thus, it is possible that using patient-derived in vitro models to screen a small and carefully selected list of compounds that inhibit key molecular targets across different glioblastoma subtypes can increase feasibility and efficiency for its rapid implementation in precision neuro-oncology [ 37 ].…”

“…For example, thus far only three tumor subtypes, four cancer stem cell transcriptional states and a few biomarker-based predictors of therapy response ( MGMT methylation and IDH1 mutation) have been described [ 37 ]. Thus, it is possible that using patient-derived in vitro models to screen a small and carefully selected list of compounds that inhibit key molecular targets across different glioblastoma subtypes can increase feasibility and efficiency for its rapid implementation in precision neuro-oncology [ 37 ]. With this in mind, we first focused on the identification of molecular targets that contribute to different biological processes in glioblastoma (invasion, cell death resistance, transition between transcriptional states, cell–ECM adhesion, cell–cell adhesion, tumor metabolism, etc.)…”

“…Our main goal was to select a repertoire of inhibitors/drugs that target a diverse set of cellular processes that contribute to glioblastoma aggressiveness (proliferation, invasion, stem cell properties, resistance to cell death, metabolism, etc.). We aimed to test the efficacy of these inhibitors using patient-derived in vitro models that better recapitulate inter- and intra-tumor heterogeneity, as well as the response to treatment [ 9 , 37 ]. This is an important consideration for the clinical management of glioblastoma as there are currently only four possible treatments that target tumor cell proliferation and angiogenesis [ 9 , 37 ], which provide limited benefits to patients [ 120 ].…”

“…We aimed to test the efficacy of these inhibitors using patient-derived in vitro models that better recapitulate inter- and intra-tumor heterogeneity, as well as the response to treatment [ 9 , 37 ]. This is an important consideration for the clinical management of glioblastoma as there are currently only four possible treatments that target tumor cell proliferation and angiogenesis [ 9 , 37 ], which provide limited benefits to patients [ 120 ]. Moreover, we restricted our analysis to inhibitors/drugs (majority small molecules) that are either FDA approved (i.e., can be repurposed to glioblastoma) or in Phase II–IV clinical trials (i.e., already passed the safety test and have shown either a favorable or heterogeneous response in patients).…”

“…This still consists of maximal surgical resection of the tumor followed by TMZ chemotherapy and radiotherapy [ 35 , 36 ]. Apart from TMZ, there are four other drugs that have been approved by FDA for glioblastoma treatment; however, they provide limited benefit to patients [ 37 ]. This reveals an urgent need for the development of better preclinical tools that facilitate rapid and efficient screening of new drugs that can then be used in the clinic.…”