however, Kilmer switched drugs in September 2017 to Lynparza
[olaparib], a PARP inhibitor that targets a mutation identified
in an earlier tissue biopsy.) Kilmer and her oncologist don’t
know if they managed to avoid a cancer recurrence, but she
says the change in medication did improve her symptoms.
With so much about liquid biopsies still unknown, traditional
molecular analysis using tumor tissue remains a mainstay. John
Nissim, who is retired and lives in Philadelphia, was diagnosed
with stage IV NSCLC in November 2014. He underwent a tissue
biopsy of a tumor in his spine and learned that the tumor had
what’s called a “classical” EGFR mutation. These tumors can
often be successfully controlled with tyrosine kinase inhibitors.
After Nissim received radiation, his oncologist prescribed
Tarceva (erlotinib). He also had two liquid biopsies, but they
didn’t reveal any new information.
In October 2017, a biopsy of cancerous adrenal tissue revealed
an additional mutation in the EGFR gene, called T790M, which
wasn’t detected in the liquid biopsies. The mutation suggested
that Nissim could have been developing resistance to Tarceva. In
December 2017, he switched to Tagrisso (osimertinib), another
tyrosine kinase inhibitor.
Improving the Science
Scientists are looking for ways to make liquid biopsies more
precise so they can be more regularly be used for monitoring
disease progression. Jerry S.H. Lee, a chemical engineer and
the health sciences director at the National Cancer Institute
in Bethesda, Maryland, develops programs aimed at using
new technologies to help improve effective cancer interventions. He notes that blood sample results depend on a staggering range of factors, such as differences in patients’ weight
or whether “a patient is taking drugs like anticoagulants that
change the composition of blood. It’s not static, like tissue.”
This leads to variability in samples. “At any given moment,
you’re hoping that what you just pulled out is representative”
of how the cancer is progressing, he says.
The human body constantly processes and breaks down
DNA—from both normally functioning cells and cancerous
ones. Each blood sample may not contain every mutation in
a cancer tumor. And even though liquid biopsies can detect
many mutations—the Cobas test identifies 42—the importance
of all those mutations in cancer progression isn’t always clear,
making liquid biopsies imprecise tools for now.
Researchers are trying to speed up the development of clinically useful liquid biopsies through collaboration. For example,
the National Cancer Moonshot Initiative, which was led by
former U.S. Vice President Joe Biden, spurred the development
of the Blood Profiling Atlas in Cancer, or BLOODPAC. This
CAN BLOOD TESTS HELP
SCREEN FOR CANCER?
The recent history of cancer diagnosis and treatment is replete with
attempts to develop sophisticated blood tests to determine whether
cancer is present. The ideal test would be able to identify patients
with existing tumors but without symptoms. The test also would need
to be reliable and not produce a lot of false positives.
In 1979, biologists identified a protein called prostate-specific
antigen (PSA) in the blood of men. (It had previously been identified
in semen and used in forensic investigations.) In 1986, the U.S. Food
and Drug Administration (FDA) approved a test to measure PSA levels
in prostate cancer patients to monitor for recurrence. In 1992, the
FDA expanded the use of the test to healthy men; high levels were
interpreted as an early warning sign of prostate cancer. The PSA test
became a screening rite of passage for men 50 and older.
However, many organs, not just the prostate, produce PSA, and high PSA
levels don’t necessarily correlate with tumor growth in the prostate.
An elevated PSA level could lead to unnecessary biopsies. Even if a
biopsy finds prostate cancer, it could lead to overtreatment if the cancer
is a slow-growing variety that is unlikely to be harmful or cause death.
For these reasons, using PSA testing to screen for prostate cancer is
Another FDA-approved blood test for cancer measures levels of CA-125, a
protein overproduced by cancers of the ovaries and fallopian tubes. At first
glance, the test appeared to be an ideal tool to screen for ovarian cancer,
which is often not identified until it’s at a late stage. However, CA-125 is
also overproduced during menstruation and by noncancerous conditions,
like uterine fibroids; the test can’t differentiate CA-125 produced by cancer
from that generated by other conditions. As a result, the CA-125 test may
be one tool among many used to track the progression of cancer, but is not
a reliable screening tool.
A liquid biopsy for cancer screening is “one of the holy grails of
cancer research,” says medical oncologist Jennifer Johnson at
Thomas Jefferson University Hospital in Philadelphia. But whether
this technology will be able to identify cancers reliably remains to
be seen. —S.O.