Recent Progress of the Tumor Microenvironmental Metabolism in Cervical Cancer Radioresistance

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Oct 31

PMID 36313645

Authors

Junying Zhou

Ningjing Lei

Wanjia Tian

Ruixia Guo

Mengyu Chen

Luojie Qiu

Fengling Wu

Yong Li

Lei Chang

Affiliations

Soon will be listed here.

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.

Citing Articles

Apoptotic cell-derived extracellular vesicles-MTA1 confer radioresistance in cervical cancer by inducing cellular dormancy.

Deng Y, Wu Q, Zhang W, Jiang H, Xu C, Chen S J Transl Med. 2025; 23(1):328.

PMID: 40087679 DOI: 10.1186/s12967-025-06350-4.

Exploring the molecular mechanism of cancer radiosensitization: the impact of physical stimulation therapy.

Liu S, Li M, Guo Z, Chen Z Strahlenther Onkol. 2025; .

PMID: 40067453 DOI: 10.1007/s00066-025-02385-0.

Elevated POSTN expression predicts poor prognosis and is associated with radioresistance in cervical cancer patients treated with radical radiotherapy.

Huang C, Xiao W, Yao X, Li Z, He J Sci Rep. 2025; 15(1):4174.

PMID: 39905145 PMC: 11794688. DOI: 10.1038/s41598-025-88908-2.

Promising predictive molecular biomarkers for cervical cancer (Review).

Lizano M, Carrillo-Garcia A, De La Cruz-Hernandez E, Castro-Munoz L, Contreras-Paredes A Int J Mol Med. 2024; 53(6).

PMID: 38606495 PMC: 11090266. DOI: 10.3892/ijmm.2024.5374.

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms.

Wang J, Mou X, Lu H, Jiang H, Xian Y, Wei X Front Endocrinol (Lausanne). 2024; 14:1302074.

PMID: 38327905 PMC: 10847243. DOI: 10.3389/fendo.2023.1302074.

References

Wilson C, Davidson S, Margison G, Jackson S, Hendry J, West C . Expression of Ku70 correlates with survival in carcinoma of the cervix. Br J Cancer. 2000; 83(12):1702-6. PMC: 2363444. DOI: 10.1054/bjoc.2000.1510. View

Tsukamoto H, Shibata K, Kajiyama H, Terauchi M, Nawa A, Kikkawa F . Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer. BMC Cancer. 2008; 8:74. PMC: 2289833. DOI: 10.1186/1471-2407-8-74. View

Kim H, Kim M, Jeong Y, Yang H . Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage. Cells. 2021; 10(9). PMC: 8465130. DOI: 10.3390/cells10092190. View

Odiase O, Noah-Vermillion L, Simone B, Aridgides P . The Incorporation of Immunotherapy and Targeted Therapy Into Chemoradiation for Cervical Cancer: A Focused Review. Front Oncol. 2021; 11:663749. PMC: 8189418. DOI: 10.3389/fonc.2021.663749. View

IJff M, van Oorschot B, Oei A, Krawczyk P, Rodermond H, Stalpers L . Enhancement of Radiation Effectiveness in Cervical Cancer Cells by Combining Ionizing Radiation with Hyperthermia and Molecular Targeting Agents. Int J Mol Sci. 2018; 19(8). PMC: 6121622. DOI: 10.3390/ijms19082420. View

Kunkel M, Moergel M, Stockinger M, Jeong J, Fritz G, Lehr H . Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity. Oral Oncol. 2007; 43(8):796-803. DOI: 10.1016/j.oraloncology.2006.10.009. View

Koukourakis M, Giatromanolaki A, Panteliadou M, Pouliliou S, Chondrou P, Mavropoulou S . Lactate dehydrogenase 5 isoenzyme overexpression defines resistance of prostate cancer to radiotherapy. Br J Cancer. 2014; 110(9):2217-23. PMC: 4007238. DOI: 10.1038/bjc.2014.158. View

Shimura T, Noma N, Sano Y, Ochiai Y, Oikawa T, Fukumoto M . AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells. Radiother Oncol. 2014; 112(2):302-7. DOI: 10.1016/j.radonc.2014.07.015. View

Gao R, Wu X, Huang Z, Wang B, Li F, Xu H . Anti-tumor effect of aloe-emodin on cervical cancer cells was associated with human papillomavirus E6/E7 and glucose metabolism. Onco Targets Ther. 2019; 12:3713-3721. PMC: 6526183. DOI: 10.2147/OTT.S182405. View

10.

Vettore L, Westbrook R, Tennant D . New aspects of amino acid metabolism in cancer. Br J Cancer. 2019; 122(2):150-156. PMC: 7052246. DOI: 10.1038/s41416-019-0620-5. View

11.

Nakamura K, Karmokar A, Farrington P, James N, Ramos-Montoya A, Bickerton S . Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control. Clin Cancer Res. 2021; 27(15):4353-4366. PMC: 9401489. DOI: 10.1158/1078-0432.CCR-20-3701. View

12.

Shanware N, Mullen A, DeBerardinis R, Abraham R . Glutamine: pleiotropic roles in tumor growth and stress resistance. J Mol Med (Berl). 2011; 89(3):229-36. DOI: 10.1007/s00109-011-0731-9. View

13.

Leung E, Cairns R, Chaudary N, Vellanki R, Kalliomaki T, Moriyama E . Metabolic targeting of HIF-dependent glycolysis reduces lactate, increases oxygen consumption and enhances response to high-dose single-fraction radiotherapy in hypoxic solid tumors. BMC Cancer. 2017; 17(1):418. PMC: 5473006. DOI: 10.1186/s12885-017-3402-6. View

14.

Zhang J, Chen M, Pang Y, Cheng M, Huang B, Xu S . Flap endonuclease 1 and DNA-PKcs synergistically participate in stabilizing replication fork to encounter replication stress in glioma cells. J Exp Clin Cancer Res. 2022; 41(1):140. PMC: 9006432. DOI: 10.1186/s13046-022-02334-0. View

15.

Huang H, Feng Y, Wan T, Zhang Y, Cao X, Huang Y . Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021; 7(3):361-369. PMC: 7809615. DOI: 10.1001/jamaoncol.2020.7168. View

16.

Huang X, Liu M, Sun H, Wang F, Xie X, Chen X . HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma. Int J Clin Exp Pathol. 2015; 8(4):4054-63. PMC: 4466980. View

17.

Liu Y, Murray-Stewart T, Casero Jr R, Kagiampakis I, Jin L, Zhang J . Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol. 2017; 50(6):2011-2023. PMC: 5435328. DOI: 10.3892/ijo.2017.3979. View

18.

Airley R, Loncaster J, Davidson S, Bromley M, Roberts S, Patterson A . Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. Clin Cancer Res. 2001; 7(4):928-34. View

19.

Zou Z, Chang H, Li H, Wang S . Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis. 2017; 22(11):1321-1335. DOI: 10.1007/s10495-017-1424-9. View

20.

Zhu Y, Qiu Y, Zhang X . TKTL1 participated in malignant progression of cervical cancer cells via regulating AKT signal mediated PFKFB3 and thus regulating glycolysis. Cancer Cell Int. 2021; 21(1):678. PMC: 8684167. DOI: 10.1186/s12935-021-02383-z. View