Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) 5 0.89, LOOCV 5 73%], CLI for CRC (AUC 5 0.98, LOOCV 5 90%), HP for small cell lung carcinoma (AUC 5 0.97, LOOCV 5 88%), C3 for lung adenocarcinoma (AUC 5 0.94, LOOCV 5 89%) and HP for squamous cell carcinoma of the lung (AUC 5 0.94, LOOCV 5 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG 1 C3 (AUC 5 0.91, LOOCV 5 83%) for breast cancer, CLI 1 HP (AUC 5 0.98, LOOCV 5 92%) for CRC, C3 1 SAA (AUC 5 0.97, LOOCV 5 91%) for small cell lung carcinoma and HP 1 SAA for both adenocarcinoma (AUC 5 0.98, LOOCV 5 96%) and squamous cell carcinoma of the lung (AUC 5 0.98, LOOCV 5 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins.Despite the recent good news that cancer incidence and death rates for men and women continue to decline in developed countries, cancer is projected to become the leading cause of death worldwide this year.1 For women, breast cancer is the most common, with lung cancer second and colorectal cancer (CRC) third.2 For men, prostate cancer is the most prevalent form of cancer, followed by lung cancer and then CRC.

Background: Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease.

Research Article 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteinsMost lung cancers are diagnosed too late for curative treatment to be possible, therefore early detection is crucial. Serum proteins are a rich source of biomarkers and have the potential to be used as diagnostic and prognostic indicators for lung cancer. In order to examine differences in serum levels of specific proteins associated with human lung squamous carcinoma, immunodepletion of albumin and five other high-abundant serum proteins followed by 2-D difference gel electrophoresis (DIGE) analysis and subsequent MS was used to generate a panel of proteins found to be differentially expressed between the cancer and normal samples. Proteins found to have increased abundance levels in squamous cell carcinoma sera compared to normal sera included apolipoprotein A-IV precursor, chain F; human complement component C3c, haptoglobin, serum amyloid A protein precursor and Ras-related protein Rab-7b. Proteins found to have lower abundance levels in squamous cell carcinoma sera compared to normal sera included alpha-2-HS glycoprotein, hemopexin precursor, proapolipoprotein, antithrombin III and SP40; 40. The data presented here demonstrate that high-abundant protein removal combined with 2-D DIGE is a powerful strategy for the discovery of potential biomarkers. The identification of lung cancer-specific biomarkers is crucial to early detection, which in turn could lead to a dramatic increase in survival rates. IntroductionOver 1 million people are diagnosed with lung cancer each year [1]. Most lung cancer is diagnosed too late for curative treatment to be possible. Efforts at early detection and treatment have had little success to date and hence the overall prognosis remains poor. In the majority of those diagnosed with lung cancer, the disease has already metastasised at the time of diagnosis. Lung cancer comprises broadly of two groups, small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). NSCLC comprises more than 80% of lung cancers including squamous cell carcinoma, adenocarcinoma and large cell carcinoma, with squamous carcinoma being the most common type.A major factor in the high mortality of lung cancer patients is the presence of metastatic tumours in approximately two-thirds of patients at time of diagnosis [2]. Detection of cancer in these patients at earlier stages would increase survival rates dramatically. The identification of lung cancer-specific biomarkers is critical to early detection. The pathophysiology of lung squamous cell carcinoma development is complex and incompletely understood. Genetic alterations involved in the pathogenesis of lung cancer produce proteins involved in cell growth, invasion/ metastasis, differentiation, cell cycle processes, apoptosis and angiogenesis. Discovering these mechanisms and pathways will undoubtedly lead to new ways in dealing with prevention, early detection an...

Insulin-like growth factor-1 receptor (IGF1R) signalling is implicated in resistance to trastuzumab. However, the benefit of co-targeting HER2 and IGF1R has not been extensively studied, and the relationship between activated IGF1R and clinical response to trastuzumab has not been reported. This study aimed to evaluate the combination of trastuzumab with IGF1R tyrosine kinase inhibitors (TKIs) in a panel of HER2-positive breast cancer cell lines, and to examine the relationship between IGF1R expression and activation and response to trastuzumab in HER2-positive breast cancer patients. The anti-proliferative effects of trastuzumab combined with IGF1R TKIs BMS-536924 or NVP-AEW541 were measured in nine HER2-positive cell lines. IGF1R and phosphorylated IGF1R/insulin receptor (pIGF1R/IR) were measured by immunohistochemistry in 160 tumour samples from trastuzumab-treated patients (ICORG 06-22). The HER2-positive cell lines displayed varying sensitivity to IGF1R TKIs alone (IC(50)s: 0.7 to >10 μM). However, when combined with trastuzumab, a significantly enhanced effect was observed in five cell lines treated with BMS-536924, and three with NVP-AEW541. While IGF1R levels correlated with reduced response to NVP-AEW541 alone, neither IGF1R nor pIGF1R were predictive of response to BMS-536924 or NVP-AEW541 in combination with trastuzumab. Low HER2 levels correlated with response to BMS-536924 in combination with trastuzumab. Akt levels correlated with improved response to trastuzumab and NVP-AEW541 (P = 0.039). Cytoplasmic IGF1R staining was observed in all tumours, membrane IGF1R was detected in 13.8 %, and pIGF1R/IR was detected in 48.8 %. Although membrane IGF1R staining was associated with larger tumour size (P = 0.041), and lower tumour grade (P = 0.024), no association between IGF1R or pIGF1R/IR and patient survival was observed. In conclusion, while neither IGF1R expression nor activation was predictive of response to trastuzumab, these pre-clinical data provide evidence that co-targeting HER2 and IGF1R may be beneficial in some HER2-amplified breast cancers.

Epirubicin 75 mg/m(2) and sulindac 600 mg are the recommended doses for phase II studies for these agents in combination.