University of Massachusetts Medical School
Faculty page: http://www.umassmed.edu/faculty/show.cfm?faculty=214
The Ross laboratory focuses on glioblastoma multiformi (GBM), which is a difficult clinical problem. Current therapy includes a combination of surgery, radiotherapy and chemotherapy. The chemotherapy drug of choice is temozolomide (TMZ) because it readily penetrates the blood-brain barrier and has manageable side effects. The inclusion of TMZ increases 2-year survival rate for GBM patients from 10.4% to 26.5%. Despite these advances, tumors in GBM patients eventually do recur. Hence, there is a great need to develop new therapies that eliminate the cells that evade current treatments.
In recent studies with Richard Moser (Neurosurgery), we have been preparing primary GBM cultures and analyzing the combination of TMZ and inhibitors of Notch signaling. This combination therapy showed enhanced efficacy in both cell culture and mouse xenograft models. In recent studies, we have found that this dual treatment may act by inducing increased senescence. We are eager to translate these methodologies to the clinic to enhance therapy and inhibit glioblastoma recurrences.
Mihaliak, A.M., Li, L., Gilbert, C.A., Daou, M.C., Moser, R.P., Reeves, A., Cochran, B.H., and Ross, A.H. 2010. Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres. Cancer Letts. 296, 168-177.
Siegelin, M.D., Plescia, J., Raskett, C.M., Gilbert, C.A., Ross, A.H., and Altieri, D.C. 2010. Global targeting of multiple subcellular pools of Hsp90 networks for glioblastoma therapy. Mol. Cancer Thera. 9, 1638-1646.
Sheng, Z., Li, L., Smith, T.W., Demers, A., Ross, A.H., Moser, R.P. and Green, M.R. 2010. A genome-wide RNA interference screen reveals an essential survival pathway in malignant gliomas. Nature Med. 16, 671-677.
Siegelin, M.D., Raskett, C., Gilbert, C.A., Ross, A.H. and Altieri, D.C. 2010. Sorafenib inhibits proliferation of glioblastoma cells in vitro and in vivo by modulation of Stat3. Neurosci. Letts. 478, 165-170.
Redfern, R.E., Daou, M.-C., Li, L., Munson, M., Gericke, A. and Ross, A.H. 2010. A mutant form of PTEN linked to autism. Protein Sci. 19, 1948-1956.
Gilbert, C.A., Daou, M.-C., Moser, R.P. and Ross, A.H. 2010. Gamma-secretase inhibitors enhance temozolomide therapy of human gliomas by inhibiting tumor repopulation and recurrence. Cancer Res. 70, 6870-6879. Chosen for press release by AACR.
Gilbert, C.A. and Ross, A.H. 2011. Glioma stem cells: cell culture, markers and targets for new combination therapies. Invited Book Chapter, Intech Press, in press.
Siegelin, M.D., Dohi, T., Raskett, C.M., Orlowski, G.M., Powers, C.M., Gilbert, C.A., Ross, A.H., Plescia, J. and Altieri, D.C. 2011. Exploitation of a mitochondrial unfolded protein response for cancer therapy in humans. J. Clin. Invest., in press.