6–10 April 2013

Walter E. Washington Convention Center Washington, DC Attendance: >18,000

The 2013 Annual Meeting of the American Association for Cancer Research (AACR) centered on the theme “Personalizing Cancer Care Through Discovery Science.” The conference brought together basic, translational and clinical approaches to studying cancer, driven by next-generation techniques. In vitro experiments, animal models and randomized trials all emphasized the goal of improving individualized care and treatment of cancer patients while maximizing contributions to our understanding of the complex pathology of cancer as a whole.

During his Plenary Session presentation, “From genes to microenvironments: cancer as an 'organismal' disease,” Siddhartha Mukherjee (Columbia University, NY) outlined how our view of cancer has shifted over time. It was originally thought to be a disease of cells, but advances in analytical technology yielded new information, causing us to revise our model. We came to see cancer as a disease of genes and then of genomes. Now, Mukherjee concluded, we must refocus our picture of cancer once again to incorporate the growing body of data suggesting that cancer is a disease of organisms.

This holistic view fits well with our increasing knowledge of cancer evolution and resistance. Kwok-Kin Wong (Dana-Farber Cancer Institute, Boston, MA) suggested in his presentation on “Mouse models of lung cancer” that cancer resistance arises from its ability to affect multiple steps or stages in signaling networks and pathways. Similarly, in his presentation, “Genetic architecture of cancer signaling pathways,” Allan Balmain (University of California San Francisco Helen Diller Family Comprehensive Cancer Center) indicated that networks, rather than genes, are the functional units in cancer signaling and that gene interactions are key in understanding the genetic architecture of cancer signaling pathways. Ross Cagan (Mount Sinai School of Medicine, New York, NY), during his presentation, “Embracing complexity: A Drosophila approach to cancer therapeutics,” further pointed out that the drivers of disease are not always the best therapeutic targets, a thought reiterated by Livio Trusolino (Institute for Cancer Research, Torino, Italy) presenting on “Colorectal cancer xenopatients: a preclinical platform for precision medicine.”

In addition to refining the definition of cancer to address networks and pathways, speakers, including Pier Paolo Pandolfi (Beth Israel Deaconess Medical Center, Boston, MA) in his presentation titled “Co-clinical trials,” reminded attendees that cancer is not one but many diseases. Identifying and characterizing the many types of cancer, and determining which drugs or therapies may work to treat each type, is the current challenge we face. In research terms, this equates to patient stratification and development of targeted therapies. Christos Sotiriou (Institut Jules Bordet, Brussels, Belgium), in a presentation on “Translational research: what is it all about?,” suggested that cancer research must move from an empirical approach (which considers primarily an 'average' patient) to a stratified one and, eventually, a personalized one.

Many of the week's presentations touched on two new paradigms in the push for personalized medicine: the master protocol and the co-clinical trial. A master protocol acts as an umbrella for multiple study arms. Trial participants are screened for a broad array of cancer biomarkers, mutations and alterations and then assigned to the study arm corresponding to their biomarker signature. This design enables rapid patient enrollment and maximizes both the information gained from each patient and the likelihood that each is matched to a study arm.

The co-clinical trial strategy aims to test potential cancer therapies in humans and in mice simultaneously, using the same protocols, and then integrate the resulting data. By synchronizing the testing, the results can be validated more rapidly in order to optimize new cancer therapies in real time.

The emergence of these platforms seems to reflect a turn away from the conventional randomized controlled trial (RCT) in treatment-focused cancer research. Several factors contribute to the declining utility of the former gold-standard RCT. The first is time: in his presentation titled “Clinical application of genome profiling in lung cancer,” Vincent Miller (Foundation Medicine, Inc., Cambridge, MA) mentioned that it takes an average of almost 8 years to develop a drug from the first preclinical work through regulatory approval. Second, the rarity of certain types of cancer can make it difficult for traditional RCTs to enroll enough participants, according to Jeffrey Abrams (National Cancer Institute, Rockville, MD) in his presentation, “Problems, successes and challenges in the research realm as we move into an era of ever more sophisticated clinical trials.” A third, related factor, pointed out Derek Raghavan (Levine Cancer Institute, Charlotte, NC) in his presentation, “Breaking through the paralysis,” is that the strictness of enrollment criteria (including cancer specificity, patient comorbidity and previous treatment history) excludes many patients.

Researchers hope that new trial designs will accelerate the discovery and testing of new therapies for cancer in order to improve patient treatment.