Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist
Ailsa J Frew, Ralph K Lindemann, Ben P Martin, Christopher JP Clarke, Janelle Sharkey, Desiree A Anthony, Kellie-Marie Banks, Nicole M Haynes, Pradnya Gangatirkar, Kym Stanley, Jessica E Bolden, Kazuyoshi Takeda, Hideo Yagita, J Paul Secrist, Mark J Smyth, Ricky W Johnstone
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2008
Histone deacetylase inhibitors (HDACi) and agents such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL receptor (TRAIL-R) antibodies are anticancer agents that have shown promise in preclinical settings and in early phase clinical trials as monotherapies. Although HDACi and activators of the TRAIL pathway have different molecular targets and mechanisms of action, they share the ability to induce tumor cell-selective apoptosis. The ability of HDACi to induce expression of TRAIL-R death receptors 4 and 5 (DR4/DR5), and induce tumor cell death via the intrinsic apoptotic pathway provides a molecular rationale to combine these agents with a..View full abstract
Related Projects (1)
Awarded by National Health and Medical Research Council (NHMRC) Program
We thank Dr. Victoria Richon (Merck) for help and advice on the project. R.W.J. is a Pfizer Australia Research Fellow and is supported by the National Health and Medical Research Council (NHMRC) Program Grant 251608, Cancer Council Victoria, Leukemia Foundation of Australia, and a research grant from Merck. A.J.F. is supported by The Cancer Research Institute Predoctoral Emphasis Pathway in Tumor Immunology. M.J.S. is a Senior Principal Research Fellow of the NHMRC and is supported by the Susan G. Komen Breast Cancer Foundation. K.T. and H.Y. are supported by the Ministry of Education, Science and Culture, Japan.