Targeting Protein Kinase C in Glioblastoma Treatment

Abstract

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCβ inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes.

Prognostic value and immune relevancy of a combined autophagy-, apoptosis- and necrosis-related gene signature in glioblastoma

“…Besides, it has also been proposed for use in patients with chronic neutrophilic leukemia for its safety and efficacy in inhibiting JAK1/2 [ 96 ]. For the low CDI group, 3 out of 7 compounds with a score higher than 90 were PKC activators, consistent with a recent study that confirmed PKC as a suitable druggable target to treat recurrent GBM [ 97 ]. The above researches demonstrated the reliability of drug screening in our study and the feasibility to applicate in GBM treatment.…”

Magnolol Induces the Extrinsic/Intrinsic Apoptosis Pathways and Inhibits STAT3 Signaling-Mediated Invasion of Glioblastoma Cells

“…Protein kinase C isoenzymes (PKCs) are a family of serine/threonine kinases to mediate phosphorylation of downstream proteins that play important roles in several oncogenic signaling pathways [35,36]. PKCδ, a member of PKCs, has been reported to potentiate STAT3 activation and result in GBM cell invasiveness [37].…”

Neurotransmitters: Potential Targets in Glioblastoma

“…It has been demonstrated that neurotransmitters have an impact on adult neurogenesis [ 15 ]. Although neurogenesis mainly occurs in the embryonic and early postnatal brain, neural stem cells (NSCs) and neural progenitor cells (NPCs) from the subventricular zone (SVZ) in the lateral ventricles and the subgranular zone (SGZ) in the dentate gyrus of the hippocampus are able to produce new neurons and glial cells in adult brains [ 18 , 19 ]. In these areas, a specific microenvironment, composed of brain microvessels surrounded by neurons and non-neurons, supports the preservation of some characteristics that are recognized as stem cell properties, such as the proliferative and self-renewal capacity of cells.…”