Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance

Abstract

Radiotherapy is widely used as an indispensable treatment option for cervical cancer patients. However, radioresistance always occurs and has become a big obstacle to treatment efficacy. The reason for radioresistance is mainly attributed to the high repair ability of tumor cells that overcome the DNA damage caused by radiotherapy, and the increased self-healing ability of cancer stem cells (CSCs). Accumulating findings have demonstrated that the tumor microenvironment (TME) is closely related to cervical cancer radioresistance in many aspects, especially in the metabolic processes. In this review, we discuss radiotherapy in cervical cancer radioresistance, and focus on recent research progress of the TME metabolism that affects radioresistance in cervical cancer. Understanding the mechanism of metabolism in cervical cancer radioresistance may help identify useful therapeutic targets for developing novel therapy, overcome radioresistance and improve the efficacy of radiotherapy in clinics and quality of life of patients.

Keywords: cervical cancer; metabolism; radioresistance; radiotherapy; tumor microenvironment.

Figure 1

The mechanism of cervical cancer radioresistance after radiotherapy. After RT, DNA double strand breaks in cervical cancer cells, and some cancer cells show apoptosis and necrosis, reaching the effect of RT. Other fraction of cancer cells has DNA damage repair (including HR and NHEJ). The wrong repair path leads to the accumulation of acquired mutations, and tumor aggressivity and recurrence, while the correct repair leads to cell survival and radioresistance. CSC, cancer stem cell; HR, homologous recombination; NHEJ, non-homologous end joining; RT, radiotherapy.

Figure 2

The role of metabolism on cervical cancer radioresistance. Glucose is transported into cells through GLUT1 for glycolysis and produces a large amount of lactic acid, enhancing cervical cancer radioresistance. Glucose in cells also produces GSH through PPP pathway. The antioxidant GSH weakens DSB after RT, resulting in radioresistance of cervical cancer cells. High expression of COX-2 in lipid metabolism and Glutamine in amino acid metabolism also contribute to cervical cancer radioresistance. GLUT1, glucose transporter 1; PPP, pentose phosphate pathway; ROS, reactive oxygen species; HIF-1, hypoxia-inducible factor 1; GSSG, oxidized glutathione; GSH, glutathione; RT, radiotherapy.