000007657 001__ 7657
000007657 005__ 20231129124934.0
000007657 0247_ $$2DOI$$a10.6083/m4qn669p
000007657 037__ $$aETD
000007657 245__ $$aLMTK3 is necessary for oncogenic signaling and survival in KIT-mutant GIST and melanoma
000007657 260__ $$bOregon Health and Science University
000007657 269__ $$a2017
000007657 336__ $$aDissertation
000007657 502__ $$bPh.D.
000007657 520__ $$aCertain cancers, including gastrointestinal stromal tumor (GIST) and subsets of melanoma, are caused by somatic KIT mutations that result in constitutive KIT receptor tyrosine kinase activity to drive neoplastic growth. The treatment of these KIT-mutant cancers has been revolutionized with the advent of KIT-directed cancer therapies. KIT tyrosine kinase inhibitors (TKI), such as imatinib, are superior to conventional chemotherapy in their ability to control advanced KIT-mutant disease. However, these therapies have a limited duration of activity due to drug-resistant secondary KIT mutations that arise (or that are selected for) during KIT TKI treatment. Once patients become resistant to KIT TKIs, GIST patients have no other options. To solve the problem of KIT TKI resistance, I sought to identify novel therapeutic targets in KIT-mutant cells using a human tyrosine kinome silencing RNA (siRNA) screen.
000007657 542__ $$fIn copyright - single owner
000007657 650__ $$aProtein-Tyrosine Kinases$$024762
000007657 650__ $$aImatinib Mesylate$$011313
000007657 650__ $$aGastrointestinal Stromal Tumors$$035784
000007657 691__ $$aSchool of Medicine$$041369
000007657 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000007657 7001_ $$aKlug, Lillian R.
000007657 8564_ $$9411bb56a-dede-418a-acee-a1247f700d57$$s24943386$$uhttps://digitalcollections.ohsu.edu/record/7657/files/Klug.Lillian.2017.pdf
000007657 905__ $$a/rest/prod/t7/22/h9/41/t722h941g
000007657 909CO $$ooai:digitalcollections.ohsu.edu:7657$$pstudent-work
000007657 980__ $$aTheses and Dissertations