December 10 2013 at 2:30 PM
The Office of the Vice President for Research is pleased to host the next Nano@Wayne seminar on Tuesday, December 10, 2013 from 2:30 to 3:30 p.m. in the Welcome Center Auditorium.The seminar is free and open to the entire campus community; a reception will immediately follow.
The guest speaker will be Dr. Larry H. Matherly, professor of oncology in WSU's School of Medicine and the Karmanos Cancer Institute. He will present, "A new paradigm for cancer therapy: exploiting the proton-coupled folate transporter for targeted drug delivery to solid tumors."
Membrane transport is essential for antitumor activity of many chemotherapy drugs used for cancer. The Matherly laboratory has long focused on studies of transport processes for folates and folate analogs. These transporters include the ubiquitously expressed reduced folate carrier (RFC), the proton-coupled folate transporter (PCFT), and the high affinity folate receptors (FRs). RFC levels and function are primary determinants of cellular uptake of folate cofactors which are essential for nucleotide biosynthesis. RFC is also a critical determinant of uptake of classic antifolate drugs used for cancer therapy such as methotrexate and newer drugs typified by pemetrexed and pralatrexate. Based on patterns of tumor-selective expression and/or function of FRs and PCFT, recent emphasis has been on identifying novel cytotoxic drugs with selective cellular uptake by these other transporters over RFC. For instance, solid tumors such as ovarian carcinomas generally express high levels of FRs, and many solid tumors including lung, ovarian, and breast cancers abundantly express PCFT. Further, tumors are characterized by acidic microenvironments which would favor membrane transport by PCFT over RFC. Based on these concepts, novel 6- substituted pyrrolo- and thieno[2,3-d]pyrimidine compounds have been synthesized and identified with excellent PCFT- and/or FR transport activity and little to no transport activity by RFC. Experiments have established extraordinarily potent antitumor activities for many of these agents. Dr. Matherly’s talk will cover the rationale for this novel approach to tumor targeting with particular focus on PCFT as a means of for selective delivery of cytotoxic chemotherapy drugs.