Can serum thioredoxin levels predict sensitivity to platinum in lung cancer?

e22062 Background: Our laboratory has found that cisplatin resistant lung cancer cells possess high levels of ROS (reactive oxygen species). Low intracellular TRX1 (thioredoxin) levels due to increased secretion of the thioredoxin-1 (TRX1) is the primary reason for high intracellular ROS levels. We have further shown that reconstituting TRX1 protein in cisplatin-resistant cells can restore sensitivity to cisplatin. Conversely, silencing TRX1 in parental cells reduced the sensitivity to cisplatin (MCT11:604, 2012). Thus, it is possible that serum TRX1 levels may be a useful marker to predict sensitivity to platinum containing regimens. Methods: Serum samples were obtained before, during, and after platinum chemotherapy. TRX1 was determined by sandwich ELISA with two TRX1 antibodies. Samples, standards, and reagent blank were incubated with precoated plate (IBL). Labeled antibody solution was added followed by Chromagen substrate and subjected to plate reader. The value on normal healthy individual is less than 5 ng/ml. The lowest limit of detection is 1 ng/ml. Results: 11 patients (pts) were entered into the study. 6 pts had small cell lung cancer (SCLC) and 5 had non small cell lung cancer (NSCLC). 2 SCLC pts died before treatment and couldn’t be assessed and 2 pts are too early to assess response. In these lung cancer pts, the baseline levels ranged from 0 to 96.5 ng/ml. Thus far, 4 pts (1 SCLC and 3 NSCLC) who had baseline TRX1 levels of 0, 0, 0 and 3 responded to chemotherapy. An additional SCLC pt with very high levels of TRX1 (96) also responded to chemotherapy. However, this pt also had a recent operation for NSCLC and the baseline blood sample was obtained after the operation, which may not be the appropriate baseline. 2 pts with baseline TRX1 levels of 31.1 and 6.5 did not respond to treatment. TRX1 levels increased during chemotherapy, especially when given concurrently with radiation. However, in pts who responded, TRX1 levels decreased at the end of treatment. Conclusions: The study is currently ongoing. Our initial results suggest that low TRX1 levels may indicate possible future response to platinum containing regimens. While TRX1 levels may increase during treatment, in pts who respond to treatment, TRX1 levels often decrease back to baseline

A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells

Aberrant activation of the Wingless-type (Wnt)/β-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi) were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer

EV-301 long-term outcomes : 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma

Abstract: Introduction: This exploratory analysis evaluated efficacy and safety data for enfortumab vedotin versus chemotherapy over a median follow-up of