LUCYREADING-IKKANDAMore recently, Gatenby’s group has
used the method in patients with meta-
static castration-resistant prostate can-
cer (mCRPC). Patients treated with the
hormone therapy abiraterone usually
progress to a drug-resistant and thus
more lethal form of the disease after
about 16 months. But instead of dosing
continuously, the Moffitt trial’s clini-
cians monitored 11 patients’ blood levels
of PSA, a biomarker for prostate can-
cer, and administered abiraterone only
until PSA had dropped to 50 percent of
its pretreatment level. Then, they sus-
pended treatment, waited a few weeks
or months until a patient’s PSA had
risen back to pretreatment levels, and
started over.
Interim findings published in 2017
indicated that, in patients exposed to
intermittent dosing, the average time
to progression to the more aggres-
sive form of the cancer was at least 27
months.^4 Last year, after expanding the
group to 15 men, the team published
an update: six had progressed, but the
rest had not, boosting the median time
to progression to at least 30 months.^5
With the trial now wrapping up after
having accrued more than 20 patients
in total, “those patients, it looks like,
are going to have about a twenty-
month increase in their median time
to progression,” says Gatenby. Plus,
“they’re getting less than half the dose
of drugs that they would have received
otherwise”—a factor that could help
reduce costs and potential side effects.
The team is now testing this approach
in patients with castration-sensitive
prostate cancer, thyroid cancer, mela-
noma, and, as of later this year, meta-
static pediatric sarcoma.
Theoretical work by the Moffitt
researchers suggests that the approach
could be more effective if clinicians use
multiple drugs to control the propor-
tions of cell subpopulations—taking
advantage, for example, of any collat-
eral sensitivities. Simulations the team
published last year indicate that repeat-
edly alternating between abiraterone
and the chemotherapy drug docetaxel
could have significantly increased time-
to-progression in the mCRPC trial,
although effective implementation of
such a regime would require precise
techniques for monitoring the propor-
tion of various tumor subpopulations.^6
(See “Tracking Changes” on page 30.)
One implication of strategies that
exploit competition among tumor sub-
populations is that they shift the goal-
posts for treatment, notes Benjamin
Roche, codirector of the Center forEcological and Evolutionary Cancer
Research in Montpellier, France. By try-
ing to maintain “competition between
resistant and sensitive cancer cells...
we are completely changing our pri-
orities about the fight against cancer,”
says Roche, who has collaborated with
Gatenby on papers in the past. “We
don’t try to remove the cancer, we try
to keep it at a low level that doesn’t kill
you... or impact your life.”
This mentality has taken a while to
percolate through the oncology com-
munity, says Gatenby. A decade ago,
the idea that clinicians might chose to
manage, rather than obliterate, a cancer
“was a difficult sell.” Understandably, heWe don’t try to remove the cancer, we try to
keep it at a low level that doesn’t kill you or
impact your life.
—Benjamin Roche, Center for Ecological and Evolutionary Cancer Research