Molecular Targeting of Glioblastoma: Drug Discovery and Therapies
A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".
Deadline for manuscript submissions: closed (30 April 2021)
Special Issue Editor
Special Issue Information
Dear Colleagues,
Glioblastoma, the deadliest brain cancer, is very challenging to cure given the limited therapeutic effects seen in clinical trials so far. Still, some illuminating examples of targeted or viral therapy resulting in exceptional responders provide hope for patients. For the large bulk of patients, however, there are currently only limited therapeutic options. A formidable challenge is therefore to find solutions to overcome the current standstill in the field.
A number of reasons can be provided for the lack of therapy effects until now. It has been observed that targeting single tumor-driving mutations such as the EGFR-VIII variant receptor by kinase inhibitors or CAR-T therapy leads to therapy resistance in most cases. Since most therapies only poorly enter the brain, poor responses can be expected. However, even taking into account that the blood–brain barrier is disturbed in some patients, thus allowing target engagement, stronger effects would have been expected. Therefore, other attenuating factors could play a role. One of the major reasons for therapy resistance is assumed to be intratumoral heterogeneity. This enables different tumor cell populations to escape therapeutic pressure. For instance, some cells escape targeted therapy because they do not depend on tumor-driving genes, resulting in the selection of cells that lack expression of this gene. A further complicating factor is the presence of the tumor microenvironment, allowing protection against the therapeutic effects as well as suppressing immune surveyance by lymphocytes.
Therefore, a number of complementary ways towards more advanced therapy strategies can be followed. This could be either through refinement of currently applied strategies or through a quest for new targets and methodologies. For instance, do multitarget kinase inhibitors provide an advantage over single-target compounds? Can drug discovery help to design better (chemo)therapeutic compounds that can reach the tumor? Is it possible to design advanced immune therapeutic approaches to activate acquired immunity locally? Is it possible to inhibit therapy resistance by targeting the tumor microenvironment? Similarly, is it possible to target therapy resistance causing residential macrophages and microglia? Is a more detailed understanding of locally cellular topology necessary to address these points? I hope that the coming decade will provide answers to these burning questions.
Dr. Bart A. Westerman
Guest Editor
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