the exact same tumor might yield contradictory
prognostic results.
This could thwart attempts to characterize a
patient’s disease based on a given biopsy, especially
given the remarkable capacity of cancer
cells to evolve in response to therapy—such that
a metastatic growth emerging after chemotherapy
may bear little genetic resemblance to the
primary tumor that spawned it. Unfortunately,
extensive sampling and analysis at different sites
is likely to be both impractical and prohibitively
costly. As an alternative, many experts believe
that pathologists should aim to collect biopsies
as close as possible to the time of analysis and
after completion of each treatment stage to
assess the current state of the tumor. “Unless
we have to work with archival samples, we are
generally making [an] assessment of the patient
in real-time,” says Chinnaiyan. This is not possible
in every case, however, and Pellini cautions
against making the perfect the enemy of the
good. “It’s okay to go back and just get the last
biopsy … because the available evidence suggests
that this is good enough to improve treatment
decisions and a lot better than where we
are today,” he says.
Heterogeneity might also be overcome in part
through extremely deep sequencing coverage.
“Even if there are lots of different cell types in
there, you may be able to capture all of those
and be able to informatically deconvolute the
data to determine the heterogeneity at the cellular
level,” says Mark Boguski, a pathologist at
Boston’s Beth Israel Deaconess Medical Center
and founder of Genome Health Solutions.
One of the biggest problems, in Swanton’s
view, is that this complex evolutionary process
may make it difficult to discover and validate
useful new biomarkers or to predict how