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, according to a new study. Most cancers begin similarly, with many possible routes to the same disease. The study found little or no overlap in the most prominent genetic malfunction associated with each individual patient’s disease compared with malfunctions shared among the group of cancer patients as a whole.
“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,” said John McDonald, PhD, of 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.”
The research was published in the journal PANCREAS (2014; doi:10.1097/MPA.0000000000000020). 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’s team compiled a list of the most aberrantly expressed genes in the cancer tissues isolated from these patients relative to adjacent normal pancreatic tissue.
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The study 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.
The researchers found that the molecular profile of each individual cancer patient was unique in terms of the most significantly disrupted genes and pathways.
“If you’re dealing with a disease like cancer that can be arrived at by multiple pathways, it makes sense that you’re not going to find that each patient has taken the same path,” McDonald said.
Although the researchers found that some genes that were commonly disrupted in all or most of the patients examined, these genes were not among the most significantly disrupted in any individual patient.
Though the study is small, it raises questions about the validity of pinpointing the most important gene or pathway underlying a disease by pooling data from multiple patients, McDonald said. He favors individual profiling as the preferred method for initiating treatment. Currently, individual profiling is limited by cost and by treatment paradigms.
“Are you going to believe what you see for one patient or are you going to say, ‘I can’t interpret that data until I group it together with 100 other patients and find what’s in common among them,’” McDonald explained. “For any given individual patient, there may be mutant genes or aberrant expression patterns that are vitally important for that person’s cancer that aren’t present in other patients’ cancers.”
