Oncology Enters Era of Genomics: Sledge Calls for Overhaul of Clinical Trials System

Shaffer
Published Online: Saturday, March 9, 2013

As the genomic era in oncology unfolds, the development of new therapeutics increasingly will involve targeting a range of mutations simultaneously, requiring a “next-generation clinical trials system” to match the advances that technology is delivering, according to George W. Sledge, Jr, MD.
Sledge told attendees at the 30th Annual Miami Breast Cancer Conference Saturday that last year marked a leap forward in understanding breast cancer as the results of many genomic analyses became available. The range of mutations uncovered in individual tumors will necessitate moving beyond battling cancer by identifying a particular molecular process, as has been the case in the targeted therapy era, to multiple driver mutations.

“We’re clearly entering a new age and that age is what I consider to be the genomic era,” said Sledge, who is chief of the Oncology Division at Stanford University School of Medicine in California and a past president of the American Society of Clinical Oncology. “This is an era of great promise. We’re at the point where we’ll be able to tell an individual what’s driving their cancer but it’s going to require a whole lot more of us.”

In developing new therapeutics, researchers will have to focus not only on qualitative mutations but also quantitative aberrations, Sledge said. “We don’t need a magic bullet, we need a magic shotgun,” he said. “We need something that can shoot pellets at a lot of different targets and do so more or less simultaneously.”

“The evaluation of that gene chip that you order will be incredibly complicated and will require a significant amount of playing out over the next decade in terms of how we use it,” he said. Sledge said genomics research has revealed that cancers can be described broadly as either “stupid” or “smart.”
Cancers that are stupid have a single dominant mutation and a small mutational load, meaning that mono-therapy will be effective and that resistance to therapy will occur rarely and along the same pathway.
In contrast, smart cancers show multiple mutational drivers with a large mutational load, requiring multi-targeted therapy to which resistance is common and occurs early in treatment.

Chronic myeloid leukemia, with bcr-abl as a target and a relatively small mutational load, is an example of a stupid cancer, Sledge said. Smart cancers with a greater mutational load include those where patients’ lifestyles play a role, such as lung cancer and melanoma."

http://www.onclive.com/conference-coverage/mbcc-2013/Oncology-Enters-Era...