Ongoing medical research shows that targeted gene therapy may help in developing future treatments of cancer. However, accurate identification of the appropriate candidates gene/pathways for a targeted therapy is crucial for success. Researchers have found that the identification of genes that are significantly enriched in a group of patients with a specific cancer versus a control group is one way in developing a successful approach. This approach does, however, not work when there are multiple molecular pathways to the same cancer, the molecular determinants of the disease may be heterogeneous among individuals and possibly go undetected by group analyses.
Most cancers begin similarly, with many possible routes to the same disease. A new study, published February 11, 2014 online edition of the journal Pancreas, funded by the Georgia Tech Foundationand the St. Joseph’s Mercy Foundation, shows that assessing the route to cancer on a case-by-case basis might make more sense than basing a patient’s cancer treatment on commonly disrupted genes and pathways.[1]
As we enter the era of targeted therapy… we may be able to optimize cancer treatments … by looking for the etiology of the disease in patients individually….
In the study, the researchers explored this appraoch in pancreatic cancer. They compared the most significantly differentially expressed genes/pathways between patients with cancer and control samples as determined by group 
versus personalized analyses. In their analysis, the researchers found little or no overlap in the most prominent genetic malfunction associated with each individual patient’s disease compared to malfunctions shared among the group of cancer patients as a whole.
Importance of personalized medicine
“This paper argues for the importance of personalized medicine, where we treat each person by looking for the etiology of the disease in patients individually,” explained John McDonald, a professor in the School of Biology at the Georgia Institute of Technology in Atlanta. “The findings have ramifications on how we might best optimize cancer treatments as we enter the era of targeted gene therapy.”
In the study, researchers collected cancer and normal tissue samples from four patients with pancreatic cancer and also analyzed data from eight other pancreatic cancer patients that had been previously reported in the scientific literature by a separate research group.
McDonald and his team of researchers compiled a list of the most aberrantly expressed genes in the cancer tissues isolated from these patients relative to adjacent normal pancreatic tissue.
The researchers found that collectively 287 genes displayed significant differences in expression in the cancers versus normal tissues. Twenty-two cellular pathways were enriched in cancer samples, with more than half related to the body’s immune response. The researchers ran statistical analyses to determine if the genes most significantly abnormally expressed on an individual patient basis were the same as those identified as most abnormally expressed across the entire group of patients.
For more information:
[1] Lili LN, Matyunina LV, Walker LD, Daneker GW, McDonald JF. Evidence for the importance of personalized molecular profiling in pancreatic cancer. Pancreas. 2014 Mar;43(2):198-211. doi: 10.1097/MPA.0000000000000020. [Article][PubMed]
Photo: John McDonald is a professor in the School of Biology at the Georgia Institute of Technology in Atlanta. Photo Courtesy: Georgia Tech. Illustration: Venn diagrams show the unique, annotated genes identified as significantly differentially expressed in the group analysis and in the personalized analysis(es) of at least 1 patient (P1: Patient 1, P2: Patient 2, P3: Patient 3, P4: Patient 4). Illustration Courtesy: Lili, et al., 2014.
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