Novel insights into the molecular origins and treatment of lung cancer

Abstract

Lung cancer is the most common and most deadly cancer worldwide. Because of the aggressive and metastatic nature of many forms of the disease, it is frequently diagnosed late and responds poorly to the therapies currently available. Although our understanding of the molecular origins and evolution of lung cancer is still incomplete, recent research has yielded several developments that may offer opportunities for new, targeted and effective therapy. In this review we first discuss the prevalence and origins of lung cancer, with emphasis on non-small-cell lung cancer and adenocarcinoma, together with current treatments and their efficacy. We then look at a selection of recent papers which between them shed new light on possible therapeutic opportunities, including a novel synthetic interaction with the Kras gene and genomic or proteomic profiling studies that may pave the way for personalized treatment for lung cancer based on specific "signatures" of protein and gene expression. Lung cancer remains the foremost cause of cancer deaths worldwide. Despite advances in both detection and treatment, diagnosis is often late and the prognosis for patients poor. Our understanding of the molecular basis and progression of lung cancer remains incomplete, hampering the design and development of more effective diagnostic tools and therapies for this devastating disease. However, the last twelve months have witnessed the publication of several studies that represent significant advances in our knowledge of lung cancer, and may represent important steps on the road to effective new therapies. In this review we aim to summarize these recent developments, and give our perspectives on the therapeutic possibilities they may offer in the future.

Figure 1

The interaction between Kras and Cdk4 genes in a mouse model of NSCLC. Although lung cells with Kras mutation or Cdk4 deletion alone are viable, the combination of both genetic alterations leads to immediate cellular senescence, potentially paving the way for a specific Cdk4 inhibitor to be used therapeutically.

Figure 2

A model for the role of HIF2α in NSCLC. Both overexpression and deletion of HIF2α may promote tumor growth, with these effects occurring through the induction of protumorigenic target genes or the downregulation of tumor suppressor target genes respectively. Adapted from Mazumdar et al.