Department of Anesthesiology, Shenzhen Longhua District Central Hospital, China.
Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
Biomed Pharmacother. 2024 Nov;180:117519. doi: 10.1016/j.biopha.2024.117519. Epub 2024 Oct 7.
More than 99 % of precancerous cervical lesions are associated with human papillomavirus (HPV) infection, with HPV types 16 and 18 (especially type 16) found in over 70 % of cervical cancer cases globally. The growth of HPV-positive cervical cancer depends on the sustained expression of the viral oncogenes E6 and E7, which are key factors in maintaining the malignant phenotype of HPV-positive tumor cells. E6 and E7 oncoproteins can cause the degradation of the tumor suppressor gene p53 and the inactivation of pRb, respectively, thereby inducing carcinogenesis. However, the inhibition of p53 and pRb cannot fully explain the oncogenic mechanism of cervical cancer. Although the development of the HPV vaccine has controlled the incidence of HPV infection, its application and widespread adoption remain limited. In addition, many developing countries cannot afford the cost of vaccines. More importantly, the vaccine only prevents HPV infection and does not provide an effective treatment for patients who are already infected or have cervical cancer. Therefore, HPV-related diseases, especially cervical cancer, remain a serious challenge. This article reviews the role of glucose metabolism changes and key molecular events in HPV-induced cervical cancer, summarizes potential targets for the treatment of cervical cancer, and provides strategies for future clinical treatment. It also offers a theoretical basis for research into cervical cancer and other HPV-related tumors. Furthermore, we discuss potential treatments for HPV-associated cervical cancer through targeted metabolic pathways and analyze the risks and challenges of current targeted glucose metabolism therapies for cervical cancer.
超过 99%的癌前宫颈病变与人类乳头瘤病毒（HPV）感染有关，HPV 类型 16 和 18（尤其是类型 16）在全球超过 70%的宫颈癌病例中发现。HPV 阳性宫颈癌的生长依赖于病毒癌基因 E6 和 E7 的持续表达，E6 和 E7 癌蛋白分别导致肿瘤抑制基因 p53 的降解和 pRb 的失活，从而诱导癌变。然而，p53 和 pRb 的抑制不能完全解释宫颈癌的致癌机制。尽管 HPV 疫苗的发展控制了 HPV 感染的发病率，但它的应用和广泛采用仍然受到限制。此外，许多发展中国家负担不起疫苗的费用。更重要的是，该疫苗只能预防 HPV 感染，而不能为已经感染或患有宫颈癌的患者提供有效治疗。因此，HPV 相关疾病，特别是宫颈癌，仍然是一个严重的挑战。本文综述了葡萄糖代谢变化和 HPV 诱导的宫颈癌中关键分子事件的作用，总结了宫颈癌治疗的潜在靶点，并为未来的临床治疗提供了策略。这也为宫颈癌和其他 HPV 相关肿瘤的研究提供了理论基础。此外，我们通过靶向代谢途径讨论了针对 HPV 相关宫颈癌的潜在治疗方法，并分析了目前针对宫颈癌的靶向葡萄糖代谢治疗的风险和挑战。
