Abstract
Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules. Their involvement in the important oncosuppressive process called mitotic catastrophe will next be discussed along with select examples of microtubule-targeting agents, which are currently explored in this respect such as benzimidazole carbamate compounds. Select microtubule-targeting agents, in particular benzimidazole carbamates, induce G2/M cell cycle arrest and mitotic catastrophe in tumor cells including GBM, resulting in phenotypically variable cell fates such as mitotic death or mitotic slippage with subsequent cell demise or permanent arrest leading to senescence. Their effect is coupled with low toxicity in normal cells and not developed chemoresistance. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy.
Highlights
Malignant tumors of the central nervous system (CNS) comprise both cases arising mostly in the brain and to a minor extent in other parts of the CNS as well as metastatic malignancies originating from other tissues and/or anatomical parts in the body
This review provided ample evidence on the complexity of glioblastoma multiforme (GBM) origin, development, and behavior, which do reflect the complicated terrain where we aspire to interfere
Viability of this concept is demonstrated by the fact that many malignant cells, including GBM, are heteroploid and intrinsically prone to the aberrant course of mitosis, activation of mitotic catastrophe (MC) and their elimination
Summary
Malignant tumors of the central nervous system (CNS) comprise both cases arising mostly in the brain and to a minor extent in other parts of the CNS as well as metastatic malignancies originating from other tissues and/or anatomical parts in the body. In the former group of conditions, the most frequently occurring are malignant gliomas (accounting for up to 80% of adult brain tumors), which are traditionally categorized according to their cellular origin, histopathological features and clinical manifestation. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM owing to their limited access via hematoencephalic barrier and/or due to the intrinsic or acquired resistance of malignant astrocytes, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy
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