Reproducibility: Has Cancer Biology Failed beyond Repair?

Abstract

Cancer is the second major cause of death worldwide, and its burden of disease increases over time. Discovering, developing, and implementing useful cancer interventions is a top priority, and pressure is high on regulatory agencies to accelerate cancer-related approvals. However, 90% to 95% of cancer drugs that enter clinical trials are not approved eventually. Worse, among the drugs licensed in the recent past, the accumulated evidence has been disappointing. These interventions typically improve surrogate endpoints but achieve minimal or no survival improvements. This is in contrast to earlier, obvious major successes achieved in oncology (e.g., in treating pediatric malignancies). Cancer biomarkers research similarly produces many thousands of publications annually but rarely translates to major tools saving lives. Why are we failing? The early steps in the translational pipeline of cancer research may be broken. Typically this research involves animals and/or tissue models. Cancer biology comprises huge networks of scientific activity involving many hard-working, well-intentioned scientists. The most exciting papers with the biggest promises easily become citation classics, among the most-cited across all science. But then, most of these papers go nowhere—no lives are saved.