000007609 001__ 7609
000007609 005__ 20240124114247.0
000007609 0247_ $$2DOI$$a10.6083/m43n22wj
000007609 037__ $$aETD
000007609 245__ $$aMicroenvironment mediated resistance to her2 targeted therapeutics in her2+ breast cancer
000007609 260__ $$bOregon Health and Science University
000007609 269__ $$a2017
000007609 336__ $$aDissertation
000007609 502__ $$bPh.D.
000007609 520__ $$aThe HER2+ subtype of breast cancer typically results from amplification of the proto-oncogene ERBB2, that causes overexpression of the mitogenic cell surface receptor kinase HER2. Absent targeted therapies, this subtype is one of the most aggressive and invasive of all the breast cancer subtypes. However, because overexpressed HER2 is often the key oncogenic driver in this subtype, it has been a successful target for clinical agents that inhibit it specifically. Trastuzumab, pertuzumab, T-DM1, and lapatinib, are all FDA approved drugs that have significantly improved progression-free survival in HER2+ patients. Despite this, long term survival benefits have been hampered by de novo or emergent resistance to these targeted agents. While cell-intrinsic secondary mutations that result in drug tolerance have been well studied, the less well understood and remarkably complex cell-extrinsic tumor microenvironment has shown a substantial capacity to cause drug resistance in otherwise drug sensitive tumor cells.
000007609 542__ $$fIn copyright - single owner
000007609 650__ $$aTumor Microenvironment$$039473
000007609 650__ $$aDrug Resistance$$018079
000007609 6531_ $$abreast cancer
000007609 691__ $$aSchool of Medicine$$041369
000007609 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000007609 7001_ $$aWatson, Spencer S.
000007609 8564_ $$9bf5ec675-4397-421b-95bb-5caedf6fed9a$$s59343833$$uhttps://digitalcollections.ohsu.edu/record/7609/files/Watson.Spencer.2017.pdf
000007609 905__ $$a/rest/prod/v1/18/rf/06/v118rf068
000007609 909CO $$ooai:digitalcollections.ohsu.edu:7609$$pstudent-work
000007609 980__ $$aTheses and Dissertations