Austin J. Combest

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PURPOSE To use genetically engineered mouse models (GEMM) and orthotopic syngeneic murine transplants (OST) to develop gene expression-based predictors of response to anticancer drugs in human tumors. These mouse models offer advantages including precise genetics and an intact microenvironment/immune system. EXPERIMENTAL DESIGN We examined the efficacy of(More)
In spite of its long history, immunotherapy of cancer has led to only a few regulatory approved treatments, starting with interleukin (IL)-2 in renal cancer and melanoma and interferon in melanoma. Sipuleucel-T was approved for castrateresistant prostate cancer in 2010 and ipilimumab and pegylated interferon-α2b in 2011 for the treatment of metastatic and(More)
BACKGROUND Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The(More)
Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability(More)
e16639 Background: Few reports have focused on global changes in cancer care. The objective of this study is to assess changes in first line therapy of NS NSCLC following publication of phase 3 data in Sept 2007 (IASLC 2007), May 2008 (Scagliotti JCO 2008) and May 2009 (ASCO 2009, 8045). METHODS Chemotherapy use in first line NS NSCLC was collected via(More)
Purpose:Anticancer drugdevelopment is inefficient, but genetically engineeredmurinemodels (GEMM) andorthotopic, syngeneic transplants (OST)of cancermayoffer advantages to in vitro andxenograft systems. Experimental Design: We assessed the activity of 16 treatment regimens in a RAS-driven, Ink4a/Arfdeficient melanoma GEMM. In addition, we tested a subset of(More)
The objectives of this study were to determine whether the midazolam clearance predicted docetaxel pharmacokinetics, CA-125 change, and response and to assess the impact of cytochrome P450 (CYP) 3A5 and ATP-binding cassette, subfamily B, member 1 (ABCB1) genotypes on docetaxel pharmacokinetics and pharmacodynamics in ovarian or primary peritoneal cancer(More)
e13064 Background: Regulatory uncertainty exists about the amount of data needed to prove biosimilarity and to extrapolate across indications. Extrapolation is especially challenging for a reference compound licensed as both an anticancer and an immunomodulating agent and where the mechanism of action may play a different role in each. However, if a(More)
101 Background: Genetic mutation testing in cancer has become standard practice with the advent of targeted therapies such as vemurafenib, crizotinib, and trastuzumab and their associated companion diagnostics. We observed a rapid uptake in BRAF mutation screening in melanoma compared to ALK mutation in NSCLC and HER2 overexpression in breast cancer.(More)