Dr Viapiano and colleagues published a paper that reports a “first in class” reagent able to inhibit signaling and reduce glioblastoma progression, in Clinical Cancer Research – a top journal of the American Association for Cancer Research. Nandhu MS, Behera P, Bhaskaran V, Longo SL, Barrera-Arenas LM, Sengupta S, Rodriguez-Gil DJ, Chiocca EA, Viapiano MS. Development of a Function-Blocking Antibody Against Fibulin-3 as a Targeted Reagent for Glioblastoma. Clin Cancer Res. 2018 Feb 15;24(4):821-833.

 

Glioblastomas (GBM) are the most common malignant tumors of the CNS.  They contain a mixture of cells and are highly invasive making them difficult to treat. Currently there is no cure and treatment is aimed at slowing the progression of the tumor.  The extracellular matrix (ECM) within these malignant gliomas has unique composition and structure resulting from proteins produced by the tumor.  Different types of GBM may contain a similar ECM composition, thus making the ECM a potential target for treatment.  Fibulin-3 is an ECM glycoprotein that is essentially absent in adult brain, but highly expressed in GBM.  The molecular heterogeneity and invasive ability of GBM cells are two major obstacles for successful therapy of these malignant brain cancers. Targeting the tumor ECM may help overcome these obstacles because ECM molecules secreted by tumor cells are necessary for invasion and relatively conserved across the tumor parenchyma. New strategies against the ECM must first identify functional domains in ECM targets and develop reagents to block those domains and disrupt signaling initiated and regulated by ECM molecules. Nandhu and colleagues developed a function-blocking antibody against a GBM-enriched ECM protein (fibulin-3) that is a "first in class" reagent able to inhibit protumoral signaling and reduce GBM progression. Anti-ECM reagents may exploit a niche that is currently underexplored, leading towards more efficient combination treatments for GBM and potentially other solid tumors.