A Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma.

Lessons Learned: Treatment with the Aurora kinase A inhibitor yields often durable disease control, but limited tumor regression, in heavily pretreated patients with unresectable malignant pleural or peritoneal mesothelioma. In a limited sample size, MYC copy-number gain or gene amplification, a candidate predictive biomarker for alisertib, did not correlate with improved response numbers or patient outcomes.

Background: Malignant mesothelioma is an aggressive disease for which few effective therapies are available.

Germline Mutation of T790M and Dual/Multiple EGFR Mutations in Patients With Lung Adenocarcinoma.

Introduction: The epidermal growth factor receptor ( T790M mutation remains one of the major mechanisms of resistance to tyrosine kinase inhibitors (TKI) treatment. Cases of T790M mutations prior to TKI treatment have been reported, but most of them were somatic mutations. In this study, we report a case of primary dual mutations containing a germline T790M mutation in a NSCLC patient.

Copper transporter CTR1 expression and tissue platinum concentration in non-small cell lung cancer.

Background: Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). We previously demonstrated that low tissue platinum concentration in NSCLC specimens was significantly associated with reduced tumor response. Furthermore, low expression of the copper transporter CTR1, a transporter of platinum uptake was associated with poor clinical outcome following platinum-based therapy in NSCLC patients.

Clinical and biomarker outcomes of the phase II vandetanib study from the BATTLE trial.

Background: The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination trial prospectively obtained serum and tumor core biopsies and randomized 255 chemorefractory non-small-cell lung cancer (NSCLC) patients into four phase II trials: erlotinib, erlotinib-bexarotene, vandetanib, or sorafenib. Herein, we report the clinical and biomarker results of the phase II vandetanib trial.

Results: Fifty-four patients received vandetanib.

Clinical outcomes and biomarker profiles of elderly pretreated NSCLC patients from the BATTLE trial.

Background: Treating elderly non-small-cell lung cancer (NSCLC) patients in the salvage setting is challenging because of concerns of intolerance to therapy. Here we report outcomes (survival and toxicity) of elderly patients on the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial.

Methods: Two hundred and fifty-five chemorefractory NSCLC patients received tumor molecular analysis, and were randomized to erlotinib, erlotinib-bexarotene, vandetanib, or sorafenib.

MicroRNA 96 is a post-transcriptional suppressor of anaplastic lymphoma kinase expression.

Anaplastic lymphoma kinase (ALK) constitutes a part of the oncogenic fusion proteins nucleophosmin-ALK and echinoderm microtubule-associated protein like 4-ALK, which are aberrantly expressed in a subset of T-cell anaplastic large-cell lymphoma and non-small-cell lung cancer, respectively. The expression of mutated, constitutively active ALK also occurs in a subset of neuroblastoma tumors. ALK is believed to play an important role in promoting tumor survival.

Phase II study of dasatinib in patients with advanced non-small-cell lung cancer.

Purpose: Src family kinases (SFKs) promote cancer progression and are commonly expressed in non-small-cell lung cancer (NSCLC), but the clinical effects of SFK inhibition in NSCLC are unknown. We conducted a phase II trial of the SFK inhibitor dasatinib for advanced NSCLC. We tested the hypotheses that the activation of epidermal growth factor receptor (EGFR) or SFK or modulation of serum cytokines may predict a response to dasatinib.

Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions.

Epidemiologic and preclinical data support the oral cancer prevention potential of green tea extract (GTE). We randomly assigned patients with high-risk oral premalignant lesions (OPL) to receive GTE at 500, 750, or 1,000 mg/m(2) or placebo thrice daily for 12 weeks, evaluating biomarkers in baseline and 12-week biopsies. The OPL clinical response rate was higher in all GTE arms (n = 28; 50%) versus placebo (n = 11; 18.

Expression of epidermal growth factor (EGF)/transforming growth factor-alpha by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice.

Epidermal growth factor receptor (EGFR) has been extensively targeted in the treatment of non-small cell lung cancer, producing responses in a small number of patients. To study the role of ligand expression in mediating response to EGFR antagonism, we injected NCI-H441 [EGFR and EGF/transforming growth factor-alpha (TGF-alpha) positive] or PC14-PE6 (EGFR positive and EGF/TGF-alpha negative) human lung adenocarcinoma cells into the lungs of nude mice. We randomized the mice to receive treatment with the EGFR tyrosine kinase inhibitors gefitinib or AEE788 or vehicle.

Clinicopathologic characteristics of the EGFR gene mutation in non-small cell lung cancer.

Background: The authors sought to define clinicopathologic features associated with mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC).

Methods: The authors evaluated surgically resected NSCLC tumors for EGFR (exons 18-21) and KRAS (codons 12-13) mutations and immunohistochemistry (EGFR, phosphorylated-EGFR, and HER2/Neu), and correlated results with clinical outcome and patient and disease features. After their analysis on 159 patients was completed, they selected a second cohort of Asian patients (n = 22) and compared EGFR mutation results to place of birth and immigration to the United States.

Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis is inhibited by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human colon cancer cells.

Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that induces apoptosis in multiple tumor cell types while sparing most normal cells. We determined the effect of ectopic Bcl-2 expression on TRAIL-induced apoptosis and whether the small molecule Bcl-2 inhibitor, HA14-1, could increase TRAIL sensitivity.

Experimental Design: SW480 human colon cancer cells were stably transfected with the PC3-Bcl-2 plasmid or vector alone.

Cyclooxygenase-2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells.

The cyclooxygenase-2 (COX-2) gene encodes an inducible enzyme that converts arachidonic acid to prostaglandins and is up-regulated in colorectal neoplasms. Evidence indicates that COX-2 may regulate apoptosis and can influence the malignant phenotype. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes and induce apoptosis in colorectal cancer cell lines, which may contribute to their antitumor effects.

Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ.

Cyclooxygenase-2 (COX-2) is an inducible enzyme that converts arachidonic acid to prostaglandins. Overexpression of the COX-2 gene in mammary glands of transgenic mice was sufficient to induce tumorigenesis. We analyzed COX-2 expression in human breast cancers (and breast cancer cell lines) and adjacent ductal carcinoma in situ (DCIS) as well as its association with HER2/neu and clinicopathological variables.

In situ hybridization assay of androgen receptor gene in hepatocarcinogenesis.

AIM:To determine the correlation between expression of androgen receptor (AR) gene and hepatocarcinogenesis.METHODS:Male SD rats were used as experimental animals and the animal model of experimental hepatocarcinoma was established by means of 3'-me-DAB administration. Androgen receptor mRNA was detected by a non-radioactive in situ hybridization assay in neoplastic and non-neoplastic liver tissues.