3) The poorly oxygenated tumor tissue creates perfect GIC niches, which induce autophagy to maintain cellular homeostasis. 2) GICs express higher level of ABC transporters which promote efflux of therapeutic compounds. Cell cycle arrest at G2 phase in GICs allows the DNA repair and further enter mitotic phase. GICs are generally resistant to therapies and mostly due to following mechanisms: 1) Enhanced DNA repair capacity.

GIC niches are most commonly to be found in tumor core regions that are lessoxygenated. GBM is characterized by extensive intratumoral hypoxia. The molecular mechanisms of resistance in glioma initiating cells (GICs). In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.Ĭarmustine (PubChem CID: 2578) Cediranib (PubChem CID: 9933475) Chemotherapy Erlotinib (PubChem CID: 176870) Gefitinib (PubChem CID: 123631) Glioblastoma Immunotherapy Irinotecan (PubChem CID: 60838) Lomustine (PubChem CID: 3950) Nanotherapy Niraparib (PubChem CID: 24958200) Olaparib (PubChem CID: 23725625) Radiotherapy Targeted therapy Temozolomide (PubChem CID: 5394) Veliparib (PubChem CID: 11960529).Ĭopyright © 2021 Elsevier Ltd. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches.

Thus, durable GBM management will require the invention of innovative treatment strategies. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%.

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