**7. Overall conclusions**

Radiosensitivity phenotypes of tumor cells are comprised of distinct, multiple responses to radiation. Glioblastoma cells exhibit responses that are both sensitive and resistant

Radiobiology of Radioresistant Glioblastoma 21

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**2** 

**Impact of Metabolic and Therapeutic** 

Glioma cells, both within solid tumors and during invasion, exist in surroundings that are subject to a variety of stresses, including metabolic and environmental stresses. Nonetheless, glioma cells survive and can even thrive under hostile conditions, such as hypoxia, nutrient deprivation, and therapeutic regimens. In order to survive, these tumor cells have to find a way to adapt to such an environment by activating certain growth factor and survival pathways while down-regulating cell death mechanisms. In fact, gliomas adapt so well that they not only survive but proliferate by creating a more hospitable environment through new blood vessel formation and dissemination, even as they endure additional stresses along the way. This chapter reviews the basic stresses that glioma cells encounter during the

Internal stresses such as hypoxia, acidity, oxidative stress, and nutrient deprivation already exist within the cellular environment of tumors while external stressors like radiation treatment and genotoxic chemotherapy only worsen the internal factors. Encountering these stresses affects the process of carcinogenesis. Gliomas, especially GBM, are highly transformed tumors that react to stresses differently than less transformed cancers. Common markers of stress will be discussed along with their roles in induction of energy conservation and cell survival in glioma. Redistribution of energy resources towards

Cellular stress can cause damage and mutations to numerous proteins, nucleic acid strands, and other macromolecules. The body has an innate reaction called the cellular stress response (CSR) to such damage. In the case of glioma and other cancers, the tumor is able to highjack the body's own machinery in order to help the cancerous cells survive usually by taking advantage of intrinsic or stress-related mutations. Thus, at times, stress may only

While the type of stress may vary, a common feature of many stresses is something referred to as the oxidative burst characterized by generation of oxidative stress and redox potential

progression of tumor formation and therapeutic interventions.

further the growth and survival of tumor cells.

**2. Types of stress on glioma and their clinical implications** 

survival pathways and away from energy-consuming processes is common.

**1. Introduction** 

**Stresses on Glioma** 

*Penn State Hershey Cancer Institute* 

*United States of America* 

**Progression and Therapy** 

Kathryn J. Huber-Keener and Jin-Ming Yang *The Pennsylvania State University College of Medicine and* 

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