William M. Grady, MD, of the Fred Hutchinson Cancer Research Center, Seattle, a member of the news planning team for the symposium, commented, “There has been considerable interest in determining whether molecular alterations in primary colorectal cancer are more accurate prognostic indicators than the tumor’s pathologic stage, which is what is currently used. In this study, by grouping the molecular alterations that are present in colorectal cancers according to the signaling pathways that they regulate, Dr. Uronis and colleagues have used a unique approach to identify molecular alterations that are predictive for recurrent cancer, not only for nonmetastatic disease but also for metastatic disease.”
“If these results can be validated, these molecular alteration patterns have the potential to be used as markers to identify which patients should receive aggressive care after surgical resection of both primary and metastatic colorectal cancer and to direct the specific chemotherapeutic agents they should receive,” Dr. Grady predicted.
A Step Toward Personalized Medicine?
Jordan Berlin, MD, Ingram Professor of Cancer Research and Clinical Director of the GI Oncology Program at Vanderbilt-Ingram Cancer Center, Nashville, said several factors “make this study interesting,” including the potential to demonstrate differential sensitivity to targeted agents according to subgroup, the use of the explant model (which maintains its characteristics across multiple generations), and the demonstration of activity with drugs such as mTOR inhibitors, which are not currently used in colorectal cancer.
“The study is preliminary, and this needs further testing, but potentially we could use this model to identify targets to hit and agents that are effective in each subgroup,” he said. “While the investigators say they hope to use this approach in the adjuvant setting, I see it as very applicable to metastatic disease, where it will be easier to apply it sooner…. If clinical trials confirm what these preclinical models show, we may be able to treat subgroups of patients differently and, in some, with surprising drugs. This may move us toward the personalized medicine that we are all using as a buzzword now.” ■
Disclosure: Drs. Grady and Berlin reported no potential conflicts of interest.
Deregulation of oncogenic signaling pathways was used to molecularly subclassify colorectal cancers into clinically relevant subgroups with both prognostic and predictive implications, in a study from the Duke Institute for Genome Sciences and Policy in Durham, North Carolina.1
“There is a need to ...