If a driver is traveling to New York City, I-95 might be their
route of choice. But they could also take I-78, I-87 or any number of alternate
routes. Most cancers begin similarly, with many possible routes to the same
disease. A new study found evidence 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.
The study 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.
"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, 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."
The research was
published February 11 online in the journal PANCREAS and was
funded by the Georgia Tech Foundation and the St. Joseph's Mercy Foundation.
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.
The study found that
collectively 287 genes displayed significant differences in expression in the
cancers vs 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. "By and large,
there appears to be a lot of individuality in terms of the molecular basis of
pancreatic cancer," said McDonald, who also serves as the director of the
Integrated Cancer Research Center and as the chief scientific officer of the
Ovarian Cancer Institute.
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.
The cost of a
molecular profiling analysis to transcribe the DNA sequences of exons -- the
parts of the genome that carry instructions for proteins -- is about $2,000
(exons account for about two percent of a cell's total DNA). That's about half
the cost of this analysis five years ago, McDonald said, and a $1,000 molecular
profiling analysis might not be far off.
"As costs
continue to come down, personalized molecular profiling will be carried out on
more cancer patients," McDonald said.
Yet cost isn't the
only limiting factor, McDonald said. Scientists and doctors have to shift their
paradigm on how they use molecular profiling to treat cancer.
"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 said. "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."
Future work in
McDonald's lab will see if this pattern of individuality is repeated in larger
studies and in patients with different cancers. The group is currently working
on a genomic profiling analysis of patients with ovarian and lung cancers.
"If there are
multiple paths, then maybe individual patients are getting cancer from
alternative routes," McDonald said. "If that's the case, we should do
personalized profiling on each patient before we make judgments on the treatment
for that patient."
Journal Reference:
1.
Loukia N. Lili, Lilya
V. Matyunina, L. DeEtte Walker, George W. Daneker, John F. McDonald. Evidence
for the Importance of Personalized Molecular Profiling in Pancreatic Cancer. Pancreas,
2014; 43 (2): 198 DOI:10.1097/MPA.0000000000000020
Posted by: Indian Biosciences and Research Institute