The answer could be in your blood.
A new DNA technology that analyzes human blood
samples has been shown to catch the disease four months earlier than
traditional methods. Cancer researcher Jimmy Lin explains how it works.
Cancer is
the ultimate killer: it can strike suddenly, move swiftly through the human
body, and change form over time to evade attackers. Plus, in many cases, it
can’t be spotted easily — it often takes many different diagnostics before it
can be identified. But what if this deadliest of assassins could be detected by
a simple blood test?
Computational
biologist and cancer researcher Jimmy Lin is one of the people working on
what’s called a “liquid biopsy.” The diagnostic that he is helping develop can
recognize the presence of disease by looking for the DNA from cancer cells (TED
Talk: A simple new blood
test detects cancer early). Lin, a TED Fellow, is the chief scientific
officer (oncology) at Natera, a
California-based company that has developed a new technology that has shown
exciting results in detecting and tracking lung cancer.
ALSO READ: Lab tests used in cancer diagnosis
Cancer cells are healthy cells that have mutated and become unhealthy
and dysfunctional.
Cancer is currently detected though one of three
methods: medical procedures (for example, a colonoscopy or a biopsy); imaging
(like a mammogram); or screening for protein biomarkers (like checking PSA
levels for prostate cancer). These techniques all have drawbacks, including the
risk of false positives, dangerous exposure to radiation, limitations in
working with all body types, pain and being highly invasive. While the key to
treating and curing cancer is early detection, says Lin, detection often doesn’t
occur until a cancer is large enough to cause symptoms, or until it’s dense or
prominent enough to see on a scan or mammogram.
Just like normal cells, all cancer cells contain DNA.
Thanks to
the genomic revolution, scientists can create precision medicines that attack
only cancer cells, and not a patient’s healthy cells, by targeting certain
genetic mutations. But the drugs aren’t infallible, in part because a single
tumor can be made up of cells of different types that have different genetic
makeups. To add difficulty: A tumor’s genetic makeup can keep changing over the
course of a disease. “Some cancers evolve faster, some slower, and sometimes
they evolve in response to treatment, exhibiting what we call ‘drug
resistance,’” says Lin. “The ability to understand how cancers change is
important, not just for diagnosis, but also for figuring out what drug
therapies to use with the patient over time. This means the therapy that you’d
give after the initial diagnosis may be different from what you’d give later.”
Old knowledge gets paired with new technology.
For more
than 40 years, physicians have known that cancer cells — which grow and die
much faster than normal cells — release fragments of DNA in the human
circulatory system when they die. Advances in genomics have made it possible to
study these genetic scraps of circulating tumor DNA (ctDNA). “By collecting a
patient’s blood and extracting and sequencing the DNA, we can generate data
that can be analyzed for cancer’s presence and makeup,” says Lin.
READ MORE: CANCER OF THE COLON
While sequencing technology makes this process possible, it’s far from
easy. Natera’s
method involves first sequencing multiple regions in a patient’s tumor. Then,
portions of the genomes of each section of tissue are sequenced to construct a phylogenetic tree,
essentially a map identifying the patient’s overall cell mutations. “With this
map, we know what to look for, and from there, we can create patient-specific
assays to measure the evolution of different mutations in their blood,” says
Lin. It’s an incredibly challenging endeavor — since practically all of the DNA
in a blood sample is from healthy cells, it can be like searching for a needle
in a haystack. “We’re typically looking for fewer than one cancerous DNA
fragment in 1,000,” Lin says.
Who to start studying?
People at high risk for cancer recurrence.
Examining the ctDNA of people from the general population would be hugely
expensive; it made sense to narrow the test group down to patients who were
statistically likely to get cancer. So researchers from University College
London and the Francis Crick Institute (also in the UK) set their sights on a
high-risk group: patients with non-small-cell lung cancer (NSCLC) who’ve had
surgical treatment to remove their cancer. If any cancer cells are left in the
body, the cancer could recur — and it does recur in an estimated 30
percent to 55 percent of patients with NSCLC.
Imagine a four-month head start in beating the disease.
In a
blind, controlled two-year study, the
scientists tracked 24 patients who had undergone surgery for NSCLC and who were
deemed cancer-free. Scientists analyzed their patients’ blood with Natera’s
sequencing technique every three to six months and subjected them to CT scans,
the traditional diagnostic used for this type of cancer. With the new sequencing
method, researchers detected cancer recurrence in patients an average of four
months — 122 days — earlier than the traditional method. “Those are 122 extra
days that doctors can have to treat cancers, which could make a huge difference
to survival, as well as 122 days less for the cancer to grow,” says Lin. “For
some patients, this could mean the difference between life and death.”
Besides aiding detection, this technology might also guide cancer
treatment. During the study, the researchers also employed the sequencing
technology in some of their subjects to see if chemotherapy was successful,
allowing them to respond more nimbly to the growth and evolution of cancerous
cells. “The potential to predict relapse at an early stage or to gain insights
into which alterations are increasing in frequency suggest that ctDNA analysis
can anticipate cancer’s next move, in a similar way to how an experienced chess
player can often predict their opponent’s next gambit,” explained oncologist
Alberto Bardelli in an article in Nature.
What’s next: tackling other cancers.
Researchers are embarking on
clinical trials testing the Natera technology’s efficacy in lung, ovarian and
breast cancer monitoring and recurrence detection. It’s way too early to talk
about a cancer-free world — and that might never be possible. Still, we should
find some hope in scientists’ creative efforts to address and challenge the
disease’s most dangerous qualities.
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