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Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson
Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson
Wayne State University Dissertations
Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …
Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish
Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish
Wayne State University Dissertations
Breast cancer is the most common cancer and the second leading
cause of cancer death in women. While ER-positive breast cancer subtypes are initially
well-managed by targeted therapies targeting estrogen signaling, many women are
suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients
who were previously successfully treated with anti-estrogen therapies worsens
overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of
a tumor may allow for the possibility …