High Kynurenine in Agressive Triple Negative African American Breast Cancer

描述(申请人提供)：我们研究计划的长期目标是减少乳腺癌对非裔美国女性的不成比例的影响，特别是那些属于三阴性亚型(即ER-、PR-和Her2-)的女性。我们方法学的指导原则是非裔美国人和欧洲美国人起源的TN乳腺癌之间存在生化差异，这些差异可以部分解释乳腺癌健康状况的差异。在这个应用中，我们建议描述犬尿氨酸代谢的一个这样的变化。在一组以非裔美国人为主的TN乳腺癌中发现了高水平的代谢物犬尿氨酸和色氨酸，临床结果很差。这些患者还表现出RAS癌基因的高表达。基于这些，我们假设，与RAS信号相关的代谢产物犬尿氨酸水平较高，可能会导致非裔美国女性发生侵袭性肿瘤，患上TN乳腺癌。此外，我们认为表征犬尿氨酸代谢在TN非裔美国人乳腺癌中的作用有助于解决乳腺癌临床预后中的种族差异问题。

DESCRIPTION (provided by applicant): The long-term objective of our research plan is to reduce the disproportionate effects of breast cancer on African American women, especially those belonging to the Triple Negative subtype (i.e., ER-, PR- and Her2-). A guiding principle of our methodology is biochemical differences exist between TN breast cancers of African American and European American origin and that these differences can explain, in part, breast cancer health disparity. In this application, we propose characterization one such alteration in Kynurenine metabolism. High levels of the metabolites Kynurenine and Tryptophan were found in a subset of TN breast cancers, predominantly African American, with poor clinical outcome. These patients also showed higher expression of the RAS oncogene. Based on these we hypothesize that higher levels of the metabolite Kynurenine in association with RAS signaling, could lead to aggressive tumors within the African American women, having TN breast cancer. Further, we propose that characterization of the role of Kynurenine metabolism in TN African American breast cancer could help address the issue of racial disparity in breast cancer clinical outcomes.