Hypoxia-Induced Apoptosis in Cancer Development

According to World Health Organization reports, cancer is the leading cause of mortality, accounting for approximately ten million deaths or 1 in 6 deaths globally. The cancer care burden is increasing, putting enormous physical, emotional, and economic pressure on individuals, families, communities, and healthcare systems worldwide (Prager et al. ESMO Open 3:e000285, 2018). Many patients are losing their lives each year due to the inaccessibility to high-standard healthcare facilities and early and proper diagnosis and treatment, especially in health systems belonging to the countries which fall under low- and mid-income categories (Alkire et al. Health Affairs (Project Hope) 37:988–996, 2018). Cancer can be cured and prevented if a proper lifestyle is maintained and a correct diagnosis and effective treatment regimen are followed. Early detection, world-class treatment, and survivorship care improve cancer patients' survival rates and life expectancy in countries with advanced systems. A variety of factors are involved in cancer progression in the human body. One of the significant factors is a low level of oxygen or hypoxia in the tumor; the pancreatic tumor with 0.3% O2 is the most severe, and the brain tumor with 1.7% O2 is the most minor (Koong et al. Int J Radiat Oncol Biol Phys 48:919–922, 2000; Rampling et al. Int J Radiat Oncol Biol Phys 29:427–431, 1994). The poor prognosis of cancer patients has been linked to hypoxia which has been proved to be the most common characteristic of solid tumors. Cancer cell metabolism promotes therapeutic resistance by inducing cell quiescence under hypoxic conditions (Semenza Oncogene 29:625–634, 2010). In tumor cells, the interaction of a complex cell-signaling network including HIF, PI3K, MAPK, and NF-kB pathways is activated by hypoxia, creating a positive and negative feedback mechanism leading to the amplification or depletion of hypoxic effects (Luo et al. BioMed Res Int 2014:409272, 2014). Hypoxia can induce or resist apoptosis or programmed cell death, one of the essential factors cancer cells must evade for their survival, growth, and continued proliferation. Whether the cell will become apoptotic or antiapoptotic depends on the severity of hypoxia (Greijer and van der Wall. J Clin Pathol 57:1009–1014, 2004). This chapter discusses in detail how hypoxia is extensively connected to apoptosis and how, under severe conditions, it can lead to the development and progression of cancer with implications for treatment for the disease.