The Cancer Stem Cell Hypothesis: A Basic and Clinical Approach to Treating Glioblastoma Multiforme
Introduction
Glioblastoma (World Health Organization grade IV glioma; GBM) is the most prevalent and malignant primary brain tumor in adults, and it is predominantly drug and radiation resistant1. Unlike many other solid tumor types, GBM extensively invades the surrounding brain, but it rarely metastasizes to other organs. Beyond its invasive nature, there are a variety of other hallmarks of GBM, including increased proliferation (likely caused by abnormal signaling by EGFR, PDGFR, and MET) and increased angiogenesis (mediated by VEGF). Additionally, GBMs, like many other solid tumors, prefer aerobic glycolysis, a phenomenon known as the …show more content…
Increasing evidence has suggested that many solid tumors, including breast cancer, pancreatic cancer, colon cancer, and gliomas are driven by a subset of “cancer stem cells”. These cancer stem cells (CSCs) share many features with their normal, noncancerous counterparts, but have broken out of the controlled cell cycle and differentiation pathway9,10. CSCs have been found to reside in specific niches within the tumor, particularly near vasculature and in central, necrotic regions (hypoxic niche). They seem to have vital roles in tumor initiation, progression, metastasis. CSCs in GBM have also been shown to be resistant to the standard chemotherapy and radiotherapy, indicating their role in disease progression11.
**It is important to note here that the CSC hypothesis does not claim that a stem cell is the cell-of-origin, which may suggest that CSCs do not adhere to all known features of normal stem cells.
Studying Cancer Stem …show more content…
Arsenic trioxide (As2O3) was show to effectively and selectively inhibit CSC growth and tumor xenograft growth by targeting the promyelocytic leukaemia (PML) protein, a protein shown to be important for CSC maintenance and survival. Importantly, As2O3 was shown to inhibit growth of CSCs but not of matched non-stem tumor cells and normal brain tissue. Though treatments such as this one have a long way to go before being put into patients, they highlight the potential of specifically targeting CSCs and how this may ultimately lead to better, more efficacious treatments for GBM. There are many similar studies being done in labs throughout the country, all in hopes of gaining a better understanding of GBM and to find treatments for the disease. The cancer stem cell hypothesis demonstrates a phenomenon that has been studied extensively in basic science. The ideas discovered in basic science are now being used to determine alternate ways to treat glioblastoma, and these treatments will hopefully be able to be used in the clinic eventually. References
1. Killock D (2015) Molecular classification of glioma. Nature Reviews Clinical Oncology 12: 502.
2. Eckel-Passow, JE et al. (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N. Engl. J. Med. 372:
Introduction
Glioblastoma (World Health Organization grade IV glioma; GBM) is the most prevalent and malignant primary brain tumor in adults, and it is predominantly drug and radiation resistant1. Unlike many other solid tumor types, GBM extensively invades the surrounding brain, but it rarely metastasizes to other organs. Beyond its invasive nature, there are a variety of other hallmarks of GBM, including increased proliferation (likely caused by abnormal signaling by EGFR, PDGFR, and MET) and increased angiogenesis (mediated by VEGF). Additionally, GBMs, like many other solid tumors, prefer aerobic glycolysis, a phenomenon known as the …show more content…
Increasing evidence has suggested that many solid tumors, including breast cancer, pancreatic cancer, colon cancer, and gliomas are driven by a subset of “cancer stem cells”. These cancer stem cells (CSCs) share many features with their normal, noncancerous counterparts, but have broken out of the controlled cell cycle and differentiation pathway9,10. CSCs have been found to reside in specific niches within the tumor, particularly near vasculature and in central, necrotic regions (hypoxic niche). They seem to have vital roles in tumor initiation, progression, metastasis. CSCs in GBM have also been shown to be resistant to the standard chemotherapy and radiotherapy, indicating their role in disease progression11.
**It is important to note here that the CSC hypothesis does not claim that a stem cell is the cell-of-origin, which may suggest that CSCs do not adhere to all known features of normal stem cells.
Studying Cancer Stem …show more content…
Arsenic trioxide (As2O3) was show to effectively and selectively inhibit CSC growth and tumor xenograft growth by targeting the promyelocytic leukaemia (PML) protein, a protein shown to be important for CSC maintenance and survival. Importantly, As2O3 was shown to inhibit growth of CSCs but not of matched non-stem tumor cells and normal brain tissue. Though treatments such as this one have a long way to go before being put into patients, they highlight the potential of specifically targeting CSCs and how this may ultimately lead to better, more efficacious treatments for GBM. There are many similar studies being done in labs throughout the country, all in hopes of gaining a better understanding of GBM and to find treatments for the disease. The cancer stem cell hypothesis demonstrates a phenomenon that has been studied extensively in basic science. The ideas discovered in basic science are now being used to determine alternate ways to treat glioblastoma, and these treatments will hopefully be able to be used in the clinic eventually. References
1. Killock D (2015) Molecular classification of glioma. Nature Reviews Clinical Oncology 12: 502.
2. Eckel-Passow, JE et al. (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N. Engl. J. Med. 372: