Hypoxia Helps Glioma to Fight Therapy

Abstract

Abstract:Despite major improvements in the surgical management the prognosis for patients bearing malignant gliomas is still dismal. Malignant gliomas are notoriously resistant to treatment and the survival time of patients is between 3-8 years for low-grade and anaplastic gliomas and 6 -12 month for glioblastoma. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumour vasculature leading to insufficient blood supply, hypoxic areas and ultimately to the formation of necrosis, a characteristic of glioblastoma. Hypoxic/necrotic tumours are more resistant to chemotherapy and radiation. Hypoxia induces either directly or indirectly (through the activation of transcription factors) changes in the biology of a tumour and its microenvironment leading to increased aggressiveness and tumour resistance to chemotherapy and radiation. This review is focused on hypoxia-induced molecular changes affecting glioma biology and therapy.3

In vivo radiation response of proneural glioma characterized by protective p53 transcriptional program and proneural-mesenchymal shift

“…Consistent with our histological data, we find that apoptotic gene expression programs are highly induced within 6 h by IR and are accompanied by a loss of expression of genes associated with cell cycle progression. Several transcripts are also highly induced that are involved in stress responses, including redox imbalances that may be important in modulating the genotoxic effect of radiation (5). A range of transcripts for secreted growth factors and cytokines are also up-regulated after radiation.…”

“…Features of the native GBM microenvironment, such as hypoxia and tumor-stroma interactions, are critical modulators of the radiation response (4)(5)(6). Additionally, interactions between GBM cells and the tumor microenvironment have been shown to affect the stem-like character of GBM cells (7), which has been linked to radioresistance (8,9).…”

STAT3 Serine 727 Phosphorylation: A Relevant Target to Radiosensitize Human Glioblastoma

“…Tumor resistance to radiation involves radioresistance of tumor cells themselves i.e. intrinsic radioresistance, as well as interactions between tumor cells and their microenvironment (2,4). Understanding the molecular mechanisms involved in GBM radioresistance might help improve GBM treatment effectiveness.…”

Livin Contributes to Tumor Hypoxia–Induced Resistance to Cytotoxic Therapies in Glioblastoma Multiforme

“…Hypoxic tumor microenvironment has long been considered as major challenge in cancer therapy and is one of the primary causes for cancer recurrence in GBM (22). Understanding the underlying mechanism governing the nature of therapeutic resistance is therefore critical and may uncover therapeutic interventions.…”