Non-Small Cell Lung Cancer: The Challenges of the Next Decade

With about 1.5 million new cases per year, lung carcinoma is the most frequent cancer in the world; it is also the first killer in adult patients, accounting for more than a fifth of deaths from cancer (Ferlay et al. 2008). It is partly preventable with smoking cessation and it is slowly decreasing in the developed countries because of the many campaigns against tobacco addiction developed in the last decades but this is not the case in developing countries. In addition, we are observing a growing amount of lung cancer in females and in the never smoker population which may represent a significant amount of lung tumors in some series (Ferlay et al. 2008). Since multiple pathways implicated in the development of lung tumors can now be better identified, several new therapeutic options may now be offered to patients. Nevertheless, the heterogeneity of non-small cell lung cancer (NSCLC) make it a particularly complex and unpredictable disease at presentation. A large number of new molecular targets are reported every year that may potentially be of interest for drug development. However, only very few targeted agents have reached the registration step up to now. There are several reasons for these frequent failures. They include (i) not predominant alterations of pathways, (ii) multiplicity of potentially predominant alterations, (iii) lack of specificity of targeted molecules, (iv) sub-optimal strategies of registration, often related to an excessive speed in the design and launch of clinical trials mostly focused on registration requirements. Thousands of teams are working on these issues worldwide but the processes of publication are not flexible. They are generally slow when any signal, positive or negative, should be published as soon as it is discovered. That is the reason why on-line journals with the fastest review process must be developed in order to ensure a large divulgation of the most recent biological and clinical data. Frontiers in Thoracic Oncology wants to offer this opportunity to the many fundamental and translational researchers who work on thoracic tumors and particularly NSCLC, the most frequent thoracic malignancy. The major fields to be considered for NSCLC in the next decade include prevention, diagnostic procedures, surgery, radiotherapy, chemotherapy, targeted agents and vaccines, and the strategic management of each lung cancer patient at different stages of the disease. Prevention is a key issue for the control of cancer. Smoking cessation in the world would prevent the majority of lung tumors. Nevertheless, up to 30% of lung cancer are diagnosed in never smokers in the developed countries and a lot remains to be explored to identify other potential agents responsible for the development of adenocarcinoma in particular. Chemoprevention in patients at high risk of development of lung cancer is another research area that has so far not been fully exploited, especially in view of the explosion of knowledge about the molecular abnormalities that have been identified in this disease. Large randomized studies performed in the 1980s and 1990s have been substantially negative, but they were mainly based on weak epidemiological assumptions rather than biological evidence. Diagnostics have considerably evolved in the last 20 years and positron emission tomography (PET) scan, endobronchial ultrasound (EBUS), and transesophageal ultrasound (EUS) are now part of an accurate preoperative assessment of potentially operable patients in most referral centers. But diagnostics also include the molecular profile of each tumor. An explosion of new targets have been observed in the last decade, several of which having already led to the development of new targeted agents (EGFR, ELM4–ALK in particular). More than half patients with lung adenocarcinoma have a single driver mutation according to the Lung Cancer Mutation Consortium (The National Lung Screening Trial Research Team, 2011). An extensive molecular profile of each tumor is becoming a standard in the most experienced centers. Proteomics are still in their early development era but they might play a major role in the very near future. On an other hand, the role of low-dose CT scan for early detection of lung cancer will probably increase in the next future since the National Cancer Screening Trial recently reported a benefit of three yearly CT scans compared to chest-X-rays in a selected population at risk (Kris et al., 2011). Abnormalities in the tissues surrounding the tumor may potentially allow identifying those micro-nodules (<1 cm) most likely to be malignant.