Clin Cancer Res
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Gastrointestinal neuroendocrine tumors (NET) are rare heterogeneous tumors that hypersecrete neuropeptides. The scarcity of good gastrointestinal NET models has limited the ability to study potential therapeutic agents. We describe and characterize the establishment of a human midgut carcinoid tumor cell line carcinoid tumor 2 (CNDT2). ⋯ The establishment of this human midgut carcinoid tumor cell line may serve as a useful model system for studying cell biology and novel targeted agents in preclinical models.
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We have investigated mechanisms of acquired resistance to the HER2 antibody trastuzumab in BT-474 human breast cancer cells. ⋯ These results are consistent with the inability of trastuzumab to block the heterodimerization of HER2 and suggest that amplification of ligand-induced activation of ErbB receptors is a plausible mechanism of acquired resistance to trastuzumab that should be investigated in primary mammary cancers.
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Angiogenesis, the growth of new vessels from preexisting vessels, is a fundamental step in tumor growth and progression. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessel formation and permeability. Overexpression of VEGF has been observed in a variety of cancers and has been associated with a worse relapse-free and overall survival. ⋯ Significant bleeding was more frequent in the chemotherapy plus bevacizumab group, 4.4% compared with 0.9% (P = 0.001). There were 15 treatment-related deaths in the chemotherapy plus bevacizumab group, including 5 due to pulmonary hemorrhage. Future and current directions include evaluation of bevacizumab in earlier stages of NSCLC, in SCLC, and in combination with other targeted agents, such as erlotinib.
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Matuzumab and panitumumab are antibodies against the epidermal growth factor receptor (EGFR) that are being evaluated in several malignancies including non-small cell lung cancer (NSCLC). In phase I trials of single-agent matuzumab in patients with EGFR-positive cancer, three tumor responses were documented in esophageal squamous cell carcinoma as well as colorectal carcinoma. A phase I trial of matuzumab in combination with paclitaxel has been reported in 18 patients with EGFR-positive advanced NSCLC. ⋯ No responses were seen in the 14 lung cancer patients evaluated; 5 of 39 patients with colorectal cancers had objective responses. A randomized phase II trial of carboplatin/paclitaxel with or without panitumumab in 166 patients with previously untreated advanced stage IIIB/IV NSCLC did not find any benefit for the panitumumab arm compared with the chemotherapy alone arm with regard to response rates, time to disease progression, or median survival time. The lack of a biomarker to identify a subset of NSCLC patients who may derive benefit from this agent limits any potential enthusiasm for further trials of panitumumab at this time in NSCLC.
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This phase 1 dose escalation study evaluated the safety and feasibility of single-dose intrapleural IFN-beta gene transfer using an adenoviral vector (Ad.IFN-beta) in patients with malignant pleural mesothelioma (MPM) and metastatic pleural effusions (MPE). ⋯ Intrapleural instillation of Ad.IFN-beta is a potentially useful approach for the generation of antitumor immune responses in MPM and MPE patients and should be investigated further for overall clinical efficacy.