May 10, 2013
Pharmacodynamic Effects and Mechanisms of Resistance to Vemurafenib in Patients With Metastatic Melanoma
K. Trunzer, A. C. Pavlick, L. Schuchter, R. Gonzalez, G. A. McArthur, T. E. Hutson, S. J. Moschos, K. T. Flaherty, K. B. Kim, J. S. Weber, P. Hersey, G. V. Long, D. Lawrence, P. A. Ott, R. K. Amaravadi, K. D. Lewis, I. Puzanov, R. S. Lo, A. Koehler, M. Kockx, O. Spleiss, A. Schell-Steven, H. N. Gilbert, L. Cockey, G. Bollag, R. J. Lee, A. K. Joe, J. A. Sosman, A. Ribas , Journal of clinical oncology , DOI: 1200/JCO.2012.44.7888
Purpose: To assess pharmacodynamic effects and intrinsic and acquired resistance mechanisms of the BRAF inhibitor vemurafenib in BRAFV600-mutant melanoma, leading to an understanding of the mechanism of action of vemurafenib and ultimately to optimization of metastatic melanoma therapy.Methods: In the phase II clinical study NP22657 (BRIM-2), patients received oral doses...
May 2, 2013
A caspase-3 'death-switch' in colorectal cancer cells for induced and synchronous tumor apoptosis in vitro and in vivo facilitates the development of minimally invasive cell death biomarkers
Simpson KL, Cawthorne C, Zhou C, Hodgkinson CL, Walker MJ, Trapani F, Kadirvel M, Brown G, Dawson MJ, Macfarlane M, Williams KJ, Whetton AD, Dive C , Simpson KL, Cawthorne C, Zhou C, Hodgkinson CL, Walker MJ, Trapani F, Kadirvel M, Brown G, Dawson MJ, Macfarlane M, Williams KJ, Whetton AD, Dive C , Volume 4:e613
Novel anticancer drugs targeting key apoptosis regulators have been developed and are undergoing clinical trials. Pharmacodynamic biomarkers to define the optimum dose of drug that provokes tumor apoptosis are in demand; acquisition of longitudinal tumor biopsies is a significant challenge and minimally invasive biomarkers are required. Considering this, we have...
May 1, 2013
Expression of PD-L1 in primary urothelial carcinoma (UC)
J. Zhang, S. I. Dickinson, N. D. Clark, A. L. Flaherty , Journal of Clinical Oncology , J Clin Oncol 31, 2013 (suppl; abstr 4541)
Background: Engagement of programmed cell death-1 (PD-1), expressed on CD8+ T cells, with it ligand PD-L1(B7H1), expressed on tumor cells, results in T cell suppression and tumor protection. Antibodies against PD-1 or PD-L1 have reported impressive anti-tumor activities in phase I/II trials and are being tested in the phase 3...
Apr 15, 2013
MERTK receptor tyrosine kinase is a therapeutic target in melanoma
J. Schlegel, M. J. Sambade, S. Sather, S. J. Moschos, A. C. Tan, A. Winges, D. Deryckere, C. C. Carson, D. G. Trembath, J. J. Tentler, S. G. Eckhardt, P. F. Kuan, R. L. Hamilton, L. M. Duncan, C. R. Miller, N. Nikolaishvili-Feinberg, B. R. Midkiff, J. Liu, W. Zhang, C. Yang, X. Wang, S. V. Frye, H. Earp , The Journal of Clinical Investigation , DOI: 10.1172/JCI67816
Metastatic melanoma is one of the most aggressive forms of cutaneous cancers. Although recent therapeutic advances have prolonged patient survival, the prognosis remains dismal. C-MER proto-oncogene tyrosine kinase (MERTK) is a receptor tyrosine kinase with oncogenic properties that is often overexpressed or activated in various malignancies. Using both protein immunohistochemistry...
Apr 15, 2013
Single cell phenotypic heterogeneity as a prognostic factor in glioblastoma
M. C. Lloyd, M. H. Madden, L. B. Nabors, R. C. Thompson, J. J. Olson, S. L. Carroll, J. Browning, T. Epstein, R. A. Gatenby, K. M. Egan , Molecular and Cellular Biology , DOI: 10.1158/1538-7445.AM2013-714
Background: Glioblastoma Multiforme (GBM) is a highly aggressive and heterogeneous disease in which survival of patients is measured only in months. Pathologic features associated with patient outcome are still incompletely understood. Until recently, phenotypic features of single cells have not been investigated due to technological limitations. However, with the advent...