000009739 001__ 9739
000009739 005__ 20240124114329.0
000009739 0247_ $$2DOI$$a10.6083/cc08hg427
000009739 037__ $$aETD
000009739 245__ $$aTargeting cancers driven by the receptor tyrosine kinase ROS1
000009739 260__ $$bOregon Health and Science University
000009739 269__ $$a2022
000009739 336__ $$aDissertation
000009739 502__ $$bPh.D.
000009739 520__ $$aGenetic aberrations that cause constitutive activation of the receptor tyrosine kinase (RTK), ROS1, can drive cancer formation. Treatment of these cancers with tyrosine kinase inhibitors (TKIs) can lead to cancer reduction in patients. While ROS1-TKIs have achieved notable success in the clinic, especially in the treatment of non-small-cell lung cancer (NSCLC), patients eventually stop responding to treatment, as seen with other forms of targeted therapy. Therapeutic resistance represents a formidable challenge to overcome as secondary alterations either in ROS1 itself or in alternative proto-oncogenes and tumor-suppressors can reduce TKI efficacy. Furthermore, we still have a rudimentary understanding of the spectrum of ROS1-independent alterations that can cause therapeutic resistance. In addition to combating resistance, an outstanding question exists as to if single point mutations in ROS1 can promote constitutive activation of the receptor like what is observed with other RTKs. If so, a need would also exist to test the efficacy of ROS1-TKIs against these alterations. Research presented in this dissertation attempts to address these unmet clinical and research needs.
000009739 542__ $$fIn copyright - single owner
000009739 650__ $$aOncogenes$$023203
000009739 650__ $$aProtein Kinase Inhibitors$$035962
000009739 650__ $$aMolecular Targeted Therapy$$039450
000009739 6531_ $$aneoplasm drug resistance
000009739 6531_ $$atyrosine kinase receptor
000009739 691__ $$aSchool of Medicine$$041369
000009739 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000009739 7001_ $$aIyer, Sudarshan R.
000009739 8564_ $$97ea43627-030e-4b11-853d-7d4c57b3313f$$s7685173$$uhttps://digitalcollections.ohsu.edu/record/9739/files/SudarshanIyer.Iyer.2022.pdf
000009739 905__ $$a/rest/prod/cc/08/hg/42/cc08hg427
000009739 909CO $$ooai:digitalcollections.ohsu.edu:9739$$pstudent-work
000009739 980__ $$aTheses and Dissertations