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Targeting Of Mediator Kinases For Cancer Therapy And Resistance Prevention, Zachary Thomas Mack
Targeting Of Mediator Kinases For Cancer Therapy And Resistance Prevention, Zachary Thomas Mack
Theses and Dissertations
Estrogen receptor (ER)-positive breast cancers make up 70% of all breast cancer incidences in the US. Cell cycle progression of ER-positive breast cancer is highly dependent on cyclin-dependent kinases (CDK) 4 and 6, the G1/S checkpoint kinases. Inhibitors of CDK4/6 have become a major addition to the clinical arsenal against ER-positive breast cancers. CDK4/6 inhibitor palbociclib (IBRANCETM) has been approved for the treatment of ER-positive breast cancers. However, palbociclib treatment eventually fails due to the development of resistance. Laboratory studies revealed several diverse mechanisms of palbociclib resistance, making universal re-sensitization difficult to achieve. However, prevention of the adaptive process that …