New direction needed for PC research

The current focus on individualised care in many different cancer indications has left pancreatic cancer (PC) behind. Patients diagnosed with this disease live no longer today than those diagnosed two decades ago, despite numerous amounts of clinical trials. Whilst there have been great advances in other cancers, with patients benefiting from targeted drugs such as Gleevec (imatinib) and Herceptin (trastuzumab), PC still remains aggressive as ever.

Published in the 26th October online edition of the Journal of Clinical Oncology (10.1200/JCO.2009.21.9022), an expert panel convened by the National Cancer Institute has issued a consensus report that discusses many aspects of developing and testing treatments in this disease, and charts a course for the next five years. The authors of the report have stressed that the recommendations be strongly considered in any clinical trial being planned for PC.

A recommendation is to design pilot studies that test potential treatments in smaller groups before proceeding to larger trials, which have previously yielded disappointing results. Decisions about which molecular targets and potential drugs to pursue will be made based on scientific evidence that will include preclinical and animal studies that better represent PC in humans.

As the report notes, a better understanding of the complex signalling pathways in pancreatic tumours and the role of the local tumour environment are needed. More sophisticated modelling systems and repositories of high-quality biological samples that can be shared among preclinical researchers are also essential. Published in the same issue the Journal of Clinical Oncology (10.1200/JCO.2009.24.2446), a study provides an example of the kinds of trials many in the field hope to avoid in the future. As has been the pattern for these studies, patients saw little or no benefit from the experimental treatment, in this case, a combination of gemcitabine and capecitabine, as compared with gemcitabine alone.

Scientists involved in clinical trials for PC are aware of the limited success, and have already begun to adopt new ideas about developing and testing treatments. Dr Philip A Philip, the report's senior author, commented: "we have to be more thoughtful and innovative in bringing forward new targeted therapies and treatment combinations." The hope is that the new strategy will ensure that resources and patient time are spent on the most promising treatments.

Separately, in findings that could help researchers focus their drug-development efforts, Massachusetts Institute of Technology cancer biologists have identified a subpopulation of cells that can give rise to PC. In mouse models, they also found that tumours can form in other, more mature pancreatic cell types, but only when they are injured or inflamed, suggesting that PC can arise from different types of cells depending on the circumstances. In future studies, the MIT researchers plan to use their mouse models to follow the molecular events that take place during PC development, and identify potential targets for drug treatments and protein markers for early diagnosis. These new mouse models could also help researchers test potential PC treatments.

Alice Rossiter - Cancer Drug News Editor