Abstract
Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived >18mo were compared to the same time points from patients who survived <14mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment.
Highlights
In the era of personalised medicine, biomarkers are required for the stratification of patients allowing therapy to be tailored
To show the utility of these methodologies we have investigated if plasma markers with clinical utility can be identified in non-small cell lung cancer (NSCLC) patients undergoing radical radiotherapy in a deliberately small cohort (3 vs 3) using a longitudinal sampling approach
We report on the proteomic analysis of samples from the prospective study, RADAR, in which patients with small cell lung cancer or NSCLC who are treated with radical radiotherapy are asked to donate blood for research into toxicity and predicting outcome to treatment
Summary
In the era of personalised medicine, biomarkers are required for the stratification of patients allowing therapy to be tailored. This could include molecular histology of disease to allow driver mutation targeted therapy, for example EGFR tyrosine kinase inhibitors for lung cancer patients (Lynch et al, 2004; Paez et al, 2004; Pao et al, 2004). Biomarkers which can be used as early markers of response to treatment would be useful in the clinic as well as in drug development, allowing. Patients therapy to be tailored as early as possible (Beretta, 2007). Monitoring prostate specific antigen levels in blood has been used for screening and monitoring progression of prostate cancer (reviewed in Lilja et al, 2008)
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