Role of hypoxia and oxidative stress in mutagenesis and metabolic reprogramming: Driving forces which induce malignancy with UV-radiation resistance

"The Hallmarks of Cancer" were first documented as six traits that cells acquire during their progression to malignancy: a) limitless proliferation potential, b) sustained angiogenesis, c) apoptosis resistance, d) self-sufficiency in growth signals, e) insensitivity to anti-growth signals and f) ability to tissue invasion and metastasize to distinct organs. Indeed, radiation resistance of tumor cells might be explained in part by a variety of DNA damage in oncogenes and/or onco-suppressors and metabolic reprogramming that are involved in signaling pathways related to cell survival. Herein, we focus our analysis on environmental conditions that play key role in enhanced cell proliferation, evasion from apoptosis and acquiring radiation resistance such as hypoxia and oxidative stress. The text will be divided into three main parts. The first will be a comprehensive introduction of role of hypoxia and oxidative stress in tumor cell radio-sensitization. The second part will address about how UV-radiation induces mutagenesis with emphasis on dysfunctions of oncogenes and onco-suppressors. The third part will cover the reprogramming of energy metabolism that accompanies cell transformation focusing on those aspects that entail UV-induced tumor microenvironment (TME). This preamble was included in order to facilitate the understanding of the ongoing debate concerning role of glycolytic pathway and mitochondria in the process of malignant cell transformation. Finally, we will explore how we might combine treatments to kill UV-resistant cancer cells.