CANCER COMMONS: BIOMEDICINE IN THE INTERNET AGE - Collaborative Computational Technologies for Biomedical Research - page 163

c. Whenever a patient responds unexpectedly to a novel therapy, it is
critical to try to understand what subtype of cancer that patient had
so that the results can be generalized to benefi t others. Such seren-
dipitous fi ndings can result from formal clinical trials (e.g., isolated
responders in a large clinical trial that failed overall) or from the “ N -
of-1” experiments that oncologists perform everyday in their prac-
tices. Again, a personal virtual biotech can be used to determine the
molecular subtype of cancer for which the putative therapy applies
and then to organize an adaptive study that attempts to validate the
fi nding in patients with that phenotype.
All patients whose treatment is being managed within Cancer Commons
are, in effect, participating in a huge, continuously running, adaptive clinical
trial that is constantly testing and refi ning both the molecular disease model
and potential treatments in a continuously improving loop. At each point in
time, patients are treated with the best available therapies for their tumors'
molecular subtype. Subtypes are then split, corresponding to responders and
nonresponders, and new subtypes are added to accommodate previously
unseen tumor types. Each patient encounter thus becomes an opportunity to
update knowledge (represented by the molecular disease model) and have it
immediately affect subsequent patient encounters. Over time, subtypes in the
disease model will be defi ned with greater and greater specifi city and will be
linked to increasingly effi cacious therapies.
This closed-loop, rapid learning approach to translational cancer research
and the platform that supports it are described in the sections that follow.
11.2 GENOME - BASED CANCER TREATMENT, CANCER
COMMONS, AND THE MOLECULAR DISEASE MODEL
Individual patient genomes—more precisely, the genomes of their tumors—
are already being used to hypothesize treatments for particular cancers. In
a recent segment on National Public Radio's Talk of the Nation program [1] ,
Dr. Harold Varmus, newly appointed Director of the National Cancer Institute
(NCI) put it this way [1] (emphasis added):
Over the [past] 30 or 40 years . . . it's become apparent that we can identify the
set of genes that play a major role in cancer. That role is played when those genes
are damaged by mutations or rejoined or amplifi ed or inappropriately expressed
in some way. . . . we're now, one by one, picking apart the insides of a cancer cell,
understanding how cancers grow, how they invade their environments, how they
metastasize. . . . We have some successes over the last 10 years of drugs that are
precisely targeted to the damage in the cancer cell that result in dramatic remis-
sions, in some cases, sustained absence of tumors. . . . while there are commonali-
ties, every cancer is different in some way . Cancers have lots of changes, and the
task for modern cancer biologists is to understand which of those [changes] is