Biomedical Engineering Reference
In-Depth Information
considered as grounds for termination of a classical trial, so there is no advan-
tage to adaptive trials when the effect is very large.)
The way out of this conundrum is through the second type of virtual
biotech, mentioned above: using personalized virtual biotech to examine, at a
deep molecular level, why a treatment failed in a particular individual. Note
that this is very similar to the problem of fi nding a new treatment for the case,
except that we now have an example of a treatment that was supposed to work
but did not. What was different about this particular disease process that dif-
ferentiates it from the cases where this treatment worked such that it was in
the molecular disease model to begin with? If we learn this—which, if it can
be learned at all, requires more or less the same machinery as creating a new
treatment—then we have learned a new distinction between subtypes of the
disease, and the molecular disease model should be updated accordingly
(regardless of whether or not we have in hand a new treatment for the new
subtype).
In sum, at each point in time, patients will be treated with the best available
therapies for their tumors' molecular subtype based on the associated (clini-
cally indicated or proposed) treatment guidelines. The power in the Cancer
Commons approach lies in the rapid feedback loop that is generated when
patients are rationally treated based on their molecular subtype, and then if
they do not respond to the experimental agent, researchers attempt to uncover
why they failed to respond and apply these fi ndings to the next patient with a
similar molecular subtype.
Studying response outliers armed with a full genomic panel also allows one
to pose interesting questions. For example, for the subset of patients who may
have responded in a trial that failed to meet its clinical endpoints: “What
disease did these people have, which was previously lumped into a broader
subclass (e.g., triple negative breast cancer) for which there might now be an
effective therapy?” “How many others have that disease?” Or, for those
patients who failed to respond in a successful trial, one can go back to the
translational scientists on whose research the molecular disease model and
proposed guidelines were based and ask: “What didn't you understand about
the disease, drug, or molecular target now that we have thousands of new
molecular data points from real cancer patients?” These questions are not
academic; they pertain to patients who have just failed therapy and are urgently
seeking new options. Answers to questions like these will lead to splitting
existing subclasses, corresponding to responders and nonresponders, or adding
new ones to accommodate previously unseen tumor types. Over time, molecu-
lar subtypes in the disease model will be defi ned with greater and greater
specifi city and linked to increasingly effi cacious therapies.
11.4
DETAILS OF THE CANCER COMMONS PLATFORM
The goal of Cancer Commons is to provide patients and physicians with the
latest information, tools, and resources they need to obtain the best possible
Search WWH ::
Custom Search