Adjuvant cisplatin-based chemotherapy is recommended for patients with stage ATM/ATR phosphorylation II–III NSCLC after radical resection according to the 7th TNM (Tumour, Nodes, Metastasis) classification [46]. Current guidelines for patients with stage III disease recommend the use of chemotherapy and radiotherapy, either sequentially or (preferably) concurrently [46]. However, treatment for stage III NSCLC is particularly challenging due

to patients’ comorbidities and tumour heterogeneity. Although treatment approaches for stage III NSCLC differ considerably between regions and centres, neoadjuvant (chemo-)radiotherapy followed by surgery remains a standard option in selected patients with resectable stage IIIA NSCLC. New drug development and research into the optimum chemo-radiation strategies for locally advanced NSCLC is also problematic due to the fact that patients are potentially curable and may not be willing to enrol in clinical trials. Novel approaches currently being investigated in stage III NSCLC include immunomodulatory strategies, agents acting on the cell cycle (e.g. aurora kinase inhibitors) and novel cytostatics [47] and [48]. ‘Window of opportunity’ trials undertaken before chemotherapy or chemo-radiotherapy may be a useful

means of testing new agents or strategies in this population. Such trials allow the efficacy of novel therapies to be investigated before the development of selleckchem resistance arising from prior therapy [49]. Although this approach raises possible ethical concerns relating to the use of an agent of indeterminate efficacy when standard therapies are available, window trials, if carefully controlled, can provide valuable Baf-A1 mw information on the activity of new treatments for NSCLC [49] and [50]. The use of radiotherapy in lung cancer has seen a number of advances in recent years, with kinetics as well as

heterogeneity of tumours being taken into account [51], [52] and [53]. Uptake of radionuclides can also vary within tumours due to differing vascularisation. This presents the possibility of targeting different parts of the tumour with varying amounts of radiation to deliver higher doses with less toxicity [54]. Further possible future developments in radiotherapy are the combination of radiotherapy with targeted agents [55], and the use of proton-based technology, since such delivery improves target volume distribution and is more lung-sparing than photon-based delivery. Imaging biomarkers such as fluorodeoxyglucose (FDG)-positron emission tomography (PET) are also likely to be used increasingly in the future to predict an early response to radiotherapy, with changes in FDG uptake by the primary tumour found to be significantly predictive for 2-year survival in stage III NSCLC during the first week of (chemo-)radiotherapy [56]. Although cytotoxics like cisplatin have been used in the treatment of NSCLC for several decades, the mechanism(s) underlying resistance to these agents are poorly understood.