TY  - GEN
N2  - Genetic 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.
DO  - 10.6083/cc08hg427
DO  - DOI
AB  - Genetic 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.
T1  - Targeting cancers driven by the receptor tyrosine kinase ROS1
DA  - 2022
AU  - Iyer, Sudarshan R.
L1  - https://digitalcollections.ohsu.edu/record/9739/files/SudarshanIyer.Iyer.2022.pdf
PB  - Oregon Health and Science University
PY  - 2022
ID  - 9739
L4  - https://digitalcollections.ohsu.edu/record/9739/files/SudarshanIyer.Iyer.2022.pdf
KW  - Oncogenes
KW  - Protein Kinase Inhibitors
KW  - Molecular Targeted Therapy
KW  - neoplasm drug resistance
KW  - tyrosine kinase receptor
TI  - Targeting cancers driven by the receptor tyrosine kinase ROS1
Y1  - 2022
L2  - https://digitalcollections.ohsu.edu/record/9739/files/SudarshanIyer.Iyer.2022.pdf
LK  - https://digitalcollections.ohsu.edu/record/9739/files/SudarshanIyer.Iyer.2022.pdf
UR  - https://digitalcollections.ohsu.edu/record/9739/files/SudarshanIyer.Iyer.2022.pdf
ER  -