Daniel W. Bowles

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The EGF receptor (EGFR)-directed monoclonal antibody cetuximab is the only targeted therapy approved for the treatment of squamous cell carcinoma of the head and neck (HNSCC) but is only effective in a minority of patients. Epithelial-to-mesenchymal transition (EMT) has been implicated as a drug resistance mechanism in multiple cancers, and the EGFR and(More)
Targeted therapy development in head and neck squamous cell carcinoma (HNSCC) is challenging given the rarity of activating mutations. Additionally, HNSCC incidence is increasing related to human papillomavirus (HPV). We sought to develop an in vivo model derived from patients reflecting the evolving HNSCC epidemiologic landscape, and use it to identify new(More)
The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to(More)
PURPOSE The objectives of the study were to evaluate the maximum tolerated dose (MTD), safety, pharmacodynamics, pharmacokinetics, and antitumor activity of PX-866 in patients with incurable cancers. EXPERIMENTAL DESIGN This was a phase I, open-label, dose-escalation study. Drug was administered orally once per day either on an intermittent (arm 1; days(More)
The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP)(More)
BACKGROUND Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for(More)
BACKGROUND This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics, and antitumour activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with docetaxel in patients with incurable solid tumours. METHODS PX-866 was administered at escalating doses (4-8 mg daily)(More)
In the last 15 years there has been a major shift in the laws governing medical use of cannabis in the United States. Corresponding with this change there has been escalating interest in the role that cannabis, commonly referred to as marijuana, and cannabinoids play in the care of patients with cancer. This review will examine cannabis' and cannabinoids'(More)
PURPOSE This first-in-human study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of single and multiple doses of TAK-441, an investigational inhibitor of the Hedgehog signaling pathway. EXPERIMENTAL DESIGN Patients with advanced, solid tumors received daily oral TAK-441 (50-1,600 mg/day); daily dose(More)