Endometrial Cancer: Genetic, Metabolic Characteristics, Therapeutic Strategies and Nanomedicine

Abstract

Background: Endometrial cancer is the fourth most common malignancy in the female population worldwide. It was estimated that 65,620 new cases and 12,590 subsequent deaths occurred in 2020 in the United States. Patients with type II and advanced endometrial cancer do not respond well to the current treatments. Therefore, endometrial cancer should be better understood in order to develop more effective treatments. Objective: To provide an overview of genetic, metabolic characteristics, therapeutic strategies and current application of nanotechnology surrounding endometrial cancer. Method: Relevant articles were retrieved from Pubmed and were systematically reviewed. Results: Hypoxia-inducible factor-1 and Von Hippel-Lindau factor participated in oncogenesis and progression of endometrial cancer, and Nrf2 was associated with oncogenesis. Various genetic alterations were found in endometrial cancer. The examination of the abnormal X chromosome inactivation may help with the diagnosis of endometrial cancer and its precancerous lesions. Some absent tumor suppressor genes, activated oncogenes were revealed by the genetically modified mouse models. Disorders in glucose and lipid metabolism were found in endometrial cancer. Current therapeutic strategies focused on the HIF-1α pathway, the mTOR pathway as well as immunotherapy. Nanotechnology showed great potential in endometrial cancer’s early diagnosis, metastasis determination and treatment. Conclusion: Endometrial cancer has been understood in various aspects, but the underlying mechanisms still remain relatively unknown, which might be the source of novel diagnostic, prognostic and therapeutic targets. Nanomedicine in endometrial cancer is poorly studied, but the current researches showed great results in treating endometrial cancer. It needs further researching.

Glycosylation and its research progress in endometrial cancer

“…80% of EC patients are estrogen-dependent type I, and are relatively young patients with accompanying metabolic syndromes, such as obesity, diabetes, hyperinsulinemia, and insulin resistance, further supporting the concept that glucose metabolic disorders promote the occurrence and development of EC [99]. Lipid metabolism disorders are also one of the high-risk factors for EC [94]. Apolipoprotein E (ApoE), an O-glycosylated glycoprotein and part of the high-density lipoprotein, showed antioxidant, anti-inflammatory, and antiatherogenic properties [100].…”

“…Glucose metabolism is closely related to tumorigenesis and development [94]. Glucose metabolism affects glycosylase and further regulates the glycosylation modifications of protein and its biological functions [95].…”

“…Lipid metabolism disorders are also one of the high-risk factors for EC [ 94 ]. Apolipoprotein E (ApoE), an O-glycosylated glycoprotein and part of the high-density lipoprotein, showed antioxidant, anti-inflammatory, and anti-atherogenic properties [ 100 ].…”

Imaging hypoxia in endometrial cancer: How and why should it be done?

“…The prognostic relevance of hypoxia in EC has been determined largely by using the expression of HIF-1α ( 12 ) and the presence of tumor necrosis ( 34 ). Although the correlation of HIF-1α with imaging estimates of hypoxia is variable ( 35 ), an association has been demonstrated in EC ( 15 ).…”

“…A poorer prognosis in patients with EC expressing HIF-1α has been demonstrated in a metaanalysis with a hazard ratio of 2.29 ( 10 ), and its link to tumor aggressiveness at other cancer sites is documented ( 11 ). Hypoxic status also has been associated with mutations of multiple genes in endometrial cancer (EC) ( 12 ). In other cancer types, driver mutations in p53, MYC and PTEN are enriched in hypoxic tumors ( 13 ) with an effect of hypoxia on mutational load ( 14 ).…”