James S. Duncan, PhD
Office Phone: 215-728-2565
Lab Phone: 215-728-2565
Protein kinases represent one the most tractable drug targets in the pursuit of new and effective cancer treatments. Although kinase inhibitors have shown great promise for the treatment of cancer, most single agent kinase inhibitor therapies have had limited clinical success due to rapid development of drug resistance. Tumors can evade drug therapy by activating compensatory protein kinase networks that promote cell growth and survival overcoming initial treatment. Therefore, combination therapies blocking these changes in kinase activity will likely be required to prevent tumor resistance in cancer.
To meet this challenge, our laboratory employs a mass spectrometry based technology that identifies protein kinases responsible for drug resistance, providing an innovative approach to rationally design new combination treatments for cancer. Using this technology, we can capture the majority of the human kinome and detect altered kinome patterns in response to kinase inhibitors currently used to treat cancer. Kinases from all major kinome subfamilies are captured including the majority of kinases implicated in cancer development and progression, as well as a significant proportion of the understudied or (un)targeted kinome. Overall, the goals of our research are to utilize this innovative approach to assess global kinome behavior and its response to small molecule inhibitors to identify previously undiscovered kinase targets leading to new and effective combination therapies to treat cancer.Description of research projects
Fox Chase Programs
- Cooper, M.J., Cox, N.J., Zimmerman, E.I,. Dewar, B.J., Duncan, J.S., Whittle, M.C., Nguyen, T.A., Jones, L.S., Ghose Roy, S., Smalley, D.M., Kuan, P.F., Richards, K.L., Christopherson, R.I., Jin, J., Frye, S.V, Johnson, G.L., Baldwin, A.S., Graves, L.M. Application of multiplexed kinase inhibitor beads to study kinome adaptations in drug-resistant leukemia. PLoS One 8:e66755, 2013.
- Graves, L.M., Duncan, J.S., Whittle, M.C., Johnson, G.L. The dynamic nature of the kinome. Biochem. J. 450:1-8, 2013. (Review)
- Duncan, J.S., Whittle, M.C., Nakamura, K., Abell, A.N., Midland, A.A., Zawistowski, J.S., Johnson, N.L., Granger, D.A., Vincent, N.J., Darr, D.B., Usary, J., Kuan, P.F., Smalley, D.M., Major, B., He, X., Hoadley, K., Zhou, B., Sharpless, N.E., Perou, C.M., Kim, W.Y., Gomez, S.M., Chen, X., Jin, J., Frye, S.V., Earp, H.S., Graves, L.M., Johnson, G.L. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple negative breast cancer. Cell 149:307-321, 2012.
- Roberts, P.J., Usary, J., Darr, D., Dillon, P.M., Pfefferle, A.D., Whittle, M.C., Duncan, J.S., Johnson, S.M., Combest, A., Jin, J., Zamboni, W.C., Johnson, G.L., Perou, C.M., Sharpless, N.E. Combined PI3K/mTOR and MEK inhibition provides broad antitumor activity in faithful murine cancer models. Clin. Cancer Res. 18:5290-5303, 2012.
- Midland, A.A., Whittle, M.C., Duncan, J.S., Abell, A.N., Nakamura, K., Zawistowski, J.S., Carey, L.A., Earp, H.S., Graves, L.M., Gomez, S.M., Johnson, G.L. Defining the expressed breast cancer kinome. Cell Res. 22:620-623, 2012.