Abstract
Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer that has not been well characterized. It accounts for less than 10% of all endometrial cancers and 80% of endometrial cancer–related deaths. Currently, staging surgery together with chemotherapy or radiotherapy, especially vaginal cuff brachytherapy, is the main treatment strategy for USC. Whole-exome sequencing combined with preclinical and clinical studies are verifying a series of effective and clinically accessible inhibitors targeting frequently altered genes, such as HER2 and PI3K3CA, in varying USC patient populations. Some progress has also been made in the immunotherapy field. The PD-1/PD-L1 pathway has been found to be activated in many USC patients, and clinical trials of PD-1 inhibitors in USC are underway. This review updates the progress of research regarding the molecular pathogenesis and putative clinical management of USC.
Highlights
Endometrial cancer (EC) is the fourth most commonly diagnosed malignancy and the seventh most common cause of cancer death in women in the United States
According to Bokhman’s 1983 model, EC is broadly classified based on histopathologic features into two categories, type I and type II, which differ in incidence, prognosis, epidemiology, molecular pathology, and clinical behavior (Table 1) [3]
The good news is that those problems are likely to be solved by molecular targeted drugs, and therapeutic agents targeting the PI3K/AKT/mTOR signaling pathway, cell cycle regulation, and the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) pathway have already been exploited in Uterine serous carcinoma (USC) (Figure 5) [73]
Summary
Endometrial cancer (EC) is the fourth most commonly diagnosed malignancy and the seventh most common cause of cancer death in women in the United States. Type I tumors, which account for 80% to 90% of all ECs, display a well-differentiated endometrioid histological phenotype and, compared with type II tumors, have a favorable prognosis, earlier onset, and higher 5-year survival rate [4]. Among the type II tumors, uterine serous carcinoma (USC) is the most common subtype. This highly aggressive variant accounts for only 10% of all ECs but 80% of all EC-associated deaths [8,9]. The. 5-year tumor-specific survival rate is 74% and 33% for early- and late-stage USC patients, respectively (and 89% and 77% for low- and high-grade EEC) [10]. Conducting studies that focus solely on this rare subtype has been a constant challenge, making it difficult to determine optimal treatment strategies [9]
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