Novel therapies hijack the blood-brain barrier to eradicate glioblastoma cancer stem cells

Research output: Contribution to journalReview article

Abstract

Glioblastoma (GBM) is amongst the most aggressive brain tumors with a dismal prognosis. Despite significant advances in the current multimodality therapy including surgery, postoperative radiotherapy (RT) and temozolomide (TMZ)-based concomitant and adjuvant chemotherapy (CT), tumor recurrence is nearly universal with poor patient outcomes. These limitations are in part due to poor drug penetration through the blood-brain barrier (BBB) and resistance to CT and RT by a small population of cancer cells recognized as tumor-initiating cells or cancer stem cells (CSCs). Though CT and RT kill the bulk of the tumor cells, they fail to affect CSCs, resulting in their enrichment and their development into more refractory tumors. Therefore, identifying the mechanisms of resistance and developing therapies that specifically target CSCs can improve response, prevent the development of refractory tumors and increase overall survival of GBM patients. Small molecule inhibitors that can breach the BBB and selectively target CSCs are emerging. In this review, we have summarized the recent advancements in understanding the GBM CSC-specific signaling pathways, the CSC-tumor microenvironment niche that contributes to CT and RT resistance and the use of novel combination therapies of small molecule inhibitors that may be used in conjunction with TMZ-based chemoradiation for effective management of GBM.

Original languageEnglish (US)
Pages (from-to)2-14
Number of pages13
JournalCarcinogenesis
Volume40
Issue number1
DOIs
StatePublished - Mar 12 2019

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Neoplastic Stem Cells
Glioblastoma
Blood-Brain Barrier
temozolomide
Radiotherapy
Neoplasms
Drug Therapy
Therapeutics
Stem Cell Niche
Tumor Microenvironment
Adjuvant Chemotherapy
Brain Neoplasms
Recurrence
Survival
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Cancer Research

Cite this

Novel therapies hijack the blood-brain barrier to eradicate glioblastoma cancer stem cells. / Vengoji, Raghupathy; Ponnusamy, Moorthy P.; Rachagani, Satyanarayana; Mahapatra, Sidharth; Batra, Surinder K.; Shonka, Nicole; Macha, Muzafar A.

In: Carcinogenesis, Vol. 40, No. 1, 12.03.2019, p. 2-14.

Research output: Contribution to journalReview article

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