Clinical Trial Keywords:
resistance to chemotherapy, osteosarcoma, soft tissue sarcomas
Dr. Loeb has active laboratory and clinical research efforts. In the laboratory, Dr. Loeb studies a gene called WT1. High levels of WT1 convey a poor prognosis for patients with osteosarcoma and soft tissue sarcomas. Dr. Loebs laboratory has shown that WT1 expression is regulated, in part, by the amount of oxygen in a tumor, and that low oxygen levels lead to higher WT1 expression, which in turn leads to an increase in the ability of tumor cells to cause new blood vessels to form. The laboratory is studying both the mechanism by which oxygen levels control WT1 expression and the way WT1 regulates blood vessel growth. In a related project, Dr. Loebs laboratory is working to identify, characterize, and therapeutically target Ewing sarcoma stem cells. Cancer stem cells are thought to be inherently resistant to chemotherapy and are thought to cause most cases of refractory or relapsed disease. In collaboration with the laboratory of Dr. Jonathan Powell, Dr. Loeb has identified one pathway, called the mTOR signaling pathway, that may be important for sarcoma stem cells to resist chemotherapy. This finding prompted the initiation of a clinical trial, led by Dr. Loeb, to test the combination of Doxil, a standard chemotherapy drug, and Temsirolimus, an inhibitor of the mTOR signaling pathway, in patients with high risk sarcomas. Future clinical trials, already being planned, will test additional means by which the inherent chemoresistance of these key cells can be overcome, hopefully leading to significant improvements in the survival of patients with recurrent or refractory sarcomas.
Savage, W.J.; DeRusso, P.A.; Resar, L.M.; Chen, A.R.; Higman, M.A.; Loeb, D.M.; Jones, R.J.; Brodsky, R.A. Treatment of hepatitis-associated aplastic anemia with high-dose cyclophosphamide. Pediatr Blood Cancer. 2007 Dec;49(7):947-951.
Loeb, D.M.; Garrett-Mayer, E.; Hobbs, R.F.; Prideaux, A.R.; Sgouros, G.; Shokek, O.; Wharam, M.D., Jr.; Scott, T.; Schwartz, C.L. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer. 2009 Jun 1;115(11):2514-2522.
Noronha, S.A.; Farrar, J.E.; Alonzo, T.A.; Gerbing, R.B.; Lacayo, N.J.; Dahl, G.V.; Ravindranath, Y.; Arceci, R.J.; Loeb, D.M. WT1 expression at diagnosis does not predict survival in pediatric AML: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2009 Dec;53(6):1136-1139.
Hobbs, R.F.; Baechler, S.; Senthamizhchelvan, S.; Prideaux, A.R.; Esaias, C.E.; Reinhardt, M.; Frey, E.C.; Loeb, D.M.; Sgouros, G. A gamma camera count rate saturation correction method for whole-body planar imaging. Phys Med Biol. 2010 Feb 7;55(3):817-831.
Hobbs, R.F.; McNutt, T.; Baechler, S.; He, B.; Esaias, C.E.; Frey, E.C.; Loeb, D.M.; Wahl, R.L.; Shokek, O.; Sgouros, G. A Treatment Planning Method for Sequentially Combining Radiopharmaceutical Therapy and External Radiation Therapy. Int J Radiat Oncol Biol Phys. 2010 Oct 13.
Loeb, D.M.; Hobbs, R.F.; Okoli, A.; Chen, A.R.; Cho, S.; Srinivasan, S.; Sgouros, G.; Shokek, O.; Wharam, M.D., Jr.; Scott, T.; Schwartz, C.L. Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma. Cancer. 2010 Dec 1;116(23):5470-5478.
Schaeffer, E.M.; Loeb, S.; Walsh, P.C. The case for open radical prostatectomy. Urol Clin North Am. 2010 Feb;37(1):49-55, Table of Contents.