FOILING CANCER TREATMENT
Sometimes anticancer drugs stop working for reasons researchers don’t entirely understand. Take
the chemotherapy drug cytarabine. It’s often the
first drug doctors prescribe to patients with a
blood cancer called acute myeloid leukemia. But
cytarabine eventually stops working for about
30 to 50 percent of AML patients, and their cancer
Researchers have looked for defects in proteins
that may be the reason cytarabine and other drugs
fail, but there still isn’t a complete understanding
of the problem, Pandolfi says. He and colleagues
now have evidence that drug resistance may stem
from problems in some of the largest and most
bountiful of the newly discovered classes of RNAs,
known as long noncoding RNAs. Researchers
have already cataloged more than 18,000 of these
“lncRNAs” (pronounced “link RNAs”).
Pandolfi and colleagues investigated how some
lncRNAs may work against cancer patients who
are counting on chemotherapy to fight their disease. “We found hundreds of new players that can
regulate response to therapy,” he says.
When the researchers boosted production
of several lncRNAs in leukemia cells, the cells
became resistant to cytarabine, Pandolfi and colleagues reported in April 2018 in Cell. They also
found that patients with AML who had higher
than normal levels of two lncRNAs experienced
a cancer recurrence sooner than people who had
lower levels of those lncRNAs.
Researchers are just beginning to understand
how these lncRNAs influence cancer and other
diseases, but Pandolfi is hopeful that someday he
and other researchers will devise ways to control
the bad actors and boost the helpful ones.
SPARKING A TUMOR’S SPREAD
MicroRNAs are barely more than 20 RNA units,
or bases, long, but they play an outsized role in
heart disease, arthritis and many other ailments.
These pip-squeaks can also lead to nerve pain
and itchiness, researchers reported last year in
Science Translational Medicine and in Neuron
(SN Online: 8/13/18).
Hundreds of clinical studies are testing people’s
blood and tissues to determine if microRNAs
can be used to help doctors better diagnose or
understand conditions ranging from asthma
and Alzheimer’s disease to schizophrenia and
traumatic brain injury. Some researchers are
beginning to develop microRNAs as drugs and
seeking ways to inhibit rogue microRNAs.
So far, the little molecules’ most firmly established roles are as promoters of and protectors
against cancer (SN: 8/28/10, p. 18). Pancreatic cancer, for example, is a deadly foe. Only 8. 5 percent
of people are still alive five years after being diagnosed with this disease, according to U.S. National
Cancer Institute statistics.
Cancer biologist Brian Lewis of the University
of Massachusetts Medical School in Worcester and
colleagues have learned that some microRNAs
spur this lethal cancer’s initial attack and help the
tumor spread from the pancreas to other organs.
MicroRNAs are mirror images of portions of
the messenger RNAs that shuttle protein-making
Fan the flame
Some short pieces of
RNA, called microRNAs,
help ignite pancreatic
cancer. Some also help
the cancer spread.