Everyone knows that cigarette smoke or inherited mutations in certain genes can promote tumorigenesis, but these only account for a small percentage of cancer cases. It is therefore the goal of epidemiologists to identify new factors that are associated with cancer and to provide laboratory researchers with tumorigenic mechanisms to investigate. Articles in this issue present some of these unexplored territories.

On page 579 of this issue, Eugenia E. Calle and Rudolf Kaaks discuss the increases in cancer incidence associated with the growing epidemic of obesity. They explain how excessive amounts of adipose tissue can alter biological activities such as insulin sensitivity or hormone production, or increase an individual's risk of developing specific types of cancer. Another epidemiologist, Miriam Poirier, describes how certain cooking techniques used in rural China might contribute to DNA damage and, eventually, oesophageal cancer (page 630).

But it's not only the epidemiolgists that are discovering new pathways to cancer. Alain Spatz and colleagues take a genetic approach, describing how X-chromosome inactivation affects oncogenes and tumour-suppressor genes. And although biochemical research in cancer cells is frequently focused on enzymatic activities such as phosphorylation or proteolysis, Besim Ogretmen and Yusuf A. Hannun (page 604) have uncovered sphingolipid signalling pathways that are altered in cancer cells.

Hitoshi Okada and Tak Mak (page 592) remind us that there are other mechanisms of cell death besides apoptosis, such as necrosis, autophagy and mitotic catastrophe. Defects in these can also promote tumour growth and might mediate drug resistance. So, perhaps it is in straying from the beaten path we will come across new, more effective approaches to cancer therapy.