Recent regulatory approval of novel treatment options has significantly expanded the therapeutic armamentarium, and the addition of these therapies has challenged clinicians to select and optimally sequence these compounds. This review will focus on examination of current guidelines and consensus building for optimal sequencing of systemic therapies for advanced or recurrent uterine leoimyosarcoma.
Over 80% of women with high-grade serous ovarian cancer (HGSOC) develop tumor resistance to chemotherapy and die of their disease. There are currently no FDA-approved agents to improve sensitivity to first-line platinum- and taxane-based chemotherapy or to PARP inhibitors. Here, we tested the hypothesis that expression of growth arrest–specific 6 (GAS6), the ligand of receptor tyrosine kinase AXL, is associated with chemotherapy response and that sequestration of GAS6 with AVB-S6–500 (AVB-500) could improve tumor response to chemotherapy and PARP inhibitors. We found that GAS6 levels in patient tumor and serum samples collected before chemotherapy correlated with ovarian cancer chemoresponse and patient survival. Compared with chemotherapy alone, AVB-500 plus carboplatin and/or paclitaxel led to decreased ovarian cancer-cell survival in vitro and tumor burden in vivo. Cells treated with AVB-500 plus carboplatin had more DNA damage, slower DNA replication fork progression, and fewer RAD51 foci than cells treated with carboplatin alone, indicating AVB-500 impaired homologous recombination (HR). Finally, treatment with the PARP inhibitor olaparib plus AVB-500 led to decreased ovarian cancer-cell survival in vitro and less tumor burden in vivo. Importantly, this effect was seen in HR-proficient and HR-deficient ovarian cancer cells. Collectively, our findings suggest that GAS6 levels could be used to predict response to carboplatin and AVB-500 could be used to treat platinum-resistant, HR-proficient HGSOC.
Implications:
GAS6/AXL is a novel target to sensitize ovarian cancers to carboplatin and olaparib. Additionally, GAS6 levels can be associated with response to carboplatin treatment.
Purpose of Review Endometrial cancer is a highly treatable cancer; however, 13 to 15% of cases recur. Traditional cytotoxic chemotherapies have produced modest results, but new treatments show promise. This information was compiled from an extensive literature search, which was completed in order to summarize current data in this review. Our objective was to describe new therapies for recurrent endometrial cancer in the last 5 years. Recent Findings New targeted therapies are being identified for advanced and recurrent endometrial cancer. Within the last 5 years, pembrolizumab and lenvatinib have improved survival in advanced or recurrent endometrial cancer. Similarly, trastuzumab has shown efficacy in HER2-producing uterine serous cancer. Summary Patients with recurrent endometrial cancer are often difficult to salvage. Traditional chemotherapy has produced poor response rates. Both immunotherapy and other targeted therapies have shown promise in recurrent disease.
ObjectiveTo determine how sociodemographic factors impact cervical cancer survival in different geographic locations in the USA.MethodsA retrospective cohort of patients with cervical cancer from January 1, 2004 to December 31, 2015 in the National Cancer Database (NCDB) was identified. Tumor characteristics as well as race, income, insurance type, and treating facility types were compared among nine geographic regions. χ2 tests and Cox regression were used to compare differences between regions; p values <0.05 were considered significant.ResultsA total of 48 787 patients were included. Survival was inferior in seven of nine regions for underinsured patients. In six regions survival was inferior for Medicaid and Medicare patients, respectively: Middle Atlantic: hazard ratio (HR) 1.25 and 1.22; South Atlantic: HR 1.41 and HR 1.22; East North Central: HR 1.36 and HR 1.25; East South Central: HR 1.37 and HR 1.25; West North Central: HR 1.67 and HR 1.42; West South Central: HR 1.44 and HR 1.46. In the Pacific region survival was inferior for Medicare patients (HR 1.35) but not inferior for Medicaid patients. Being uninsured was associated with worse survival in the South Atlantic (HR 1.23), East North Central (HR 1.23), East South Central (HR 1.56), and West South Central (HR 1.31) regions. Annual income level under $38 000 was associated with worse survival in the Middle Atlantic (HR 1.24), South Atlantic (HR 1.35), and East North Central (HR 1.49) regions. Lastly, when compared with academic research institutions, comprehensive community cancer centers had significantly worse survival in four of the nine regions.ConclusionsCervical cancer mortality is higher for women with a low income, underinsured (Medicaid or Medicare) or uninsured status, and decreased access to academic institutions in most US regions. An increase in cervical cancer mortality was associated with underinsured or uninsured populations in regions mainly located in the South and Midwest.
Assessing albumin level, medical comorbidity, and medication type for the development of postoperative menopausal symptoms is a valuable step in the preoperative management of women with endometrial cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.