Professor Repasky's studies are aimed at understanding the role of pancreatic cancer stem cells in resistance to immune cell killing, and in particular, their sensitivity to Apo2L/TRAIL, a targeted therapy based on the molecule naturally expressed on activated T lymphocytes which can specifically cause tumor cell death by apoptosis. The lab has found that patient tumor xenografts exhibit a wide range of responses, from extremely sensitive to extremely resistant to therapies targeting cell surface death receptors. The response however, can be enhanced by combining Apo2L/TRAIL with chemotherapy. The lab has observed that even in cases where the tumors undergo regression and remained sensitive to retreatment, tumors can regrow when treatment is ended. The identification of pancreatic cancer stem cells led her lab to the intriguing speculation that cancer stem cells within these tumors may be particularly resistant to Apo2L/ TRAIL, surviving and repopulating a recurring tumor. This is a critical question because although cancer stem cells have been identified in many tumor types and it has been found that CSCs can be resistant to chemotherapy and radiation, their response to therapies targeting death receptors as well as the significance of CSCs in the clinical treatment of malignancies is, as yet, unknown.
McAllister, S.S., Gifford, A.M., Greiner, A.L., Kelleher, S.P., Saelzler, M.P., Ince, T.A., Reinhardt, F., Harris, L.N., Hylander, B.L., Repasky, E.A. and Weinberg, R.A. 2008. Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell. 2008 June 13; 133 (6): 994-1005.
Hylander BL, Pitoniak R, Penetrante RB, Gibbs JF, Oktay D, Cheng J, Repasky EA. The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice. J Transl Med. 2005 May 19;3(1):22.
Naka T, Sugamura K, Hylander BL, Widmer MB, Rustum YM, Repasky EA. Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice. Cancer Res. 2002 Oct 15;62(20):5800-6.