Ovarian cancer: New drug may prevent recurrence

middle aged cancer survivor looking at camera

By Ana Sandoiu 
Fact checked by Paula Field
New
research in mice identifies a compound that prevents ovarian cancer recurrence
by eradicating the cancer stem-like cells that conventional chemotherapy leaves
behind.
According
to the National Cancer Institute, there were over 22,000 new cases of ovarian
cancer in the United States in 2018. More than 14,000 of these resulted in
death.
Ovarian
cancer is not very common, but its recurrence rate is notoriously high.
According to previous estimates, “between 70 and 90 percent of all women
with ovarian cancer” will have a recurrence at some point after their
diagnosis, depending on how advanced the disease was.
While
a person’s outlook depends on various factors, just under 50 percent of those
who develop ovarian cancer go on to survive for 5 years, according to more
recent data.
New
research, however, may have found a way to prevent ovarian cancer from coming
back. A team of scientists, led by Dr. Ronald Buckanovich, who is also a
professor of medicine at the University of Pittsburgh in Pennsylvania,
discovered a drug that targets stem-like ovarian cancer cells and stops the
cancer from returning.
Dr.
Buckanovich and his colleagues published their findings in the journal Cell
Reports.
Plucking the root of ovarian cancer
Dr.
Buckanovich explains that, even though chemotherapy can destroy up to 99 percent
of ovarian cancer cells, the treatment still “misses” stem-like
cancer cells.
“You
can think of stem-like cells as seeds,” explains Dr. Buckanovich, who is
also the co-director of the Women’s Cancer Research Center at Pittsburgh
University. “They put down roots and grow into a plant,” he says.
“I
especially like the dandelion analogy. When we treat cancer, we’re essentially
mowing the lawn. But the problem is that dandelions always come back.”
The
researcher also explains that 11 stem-like cancer cells are enough to form a
tumor. So, the researchers set out to find a compound that can eradicate these
stem-like cells.
To
do so, the scientists carried out a range of chemical experiments.
Specifically, they aimed to find a compound that inhibits a pathway known as
ALDHA. The cancer cells rely on this pathway to get rid of the toxins that they
produce when they replicate quickly.
Study
co-author Edward Grimley, Ph.D., who is a Postdoctoral Research Associate in
the lab of Dr. Buckanovich, spoke to Medical News Today about the methods the
researchers used to find the ALDHA-inhibitor.
Grimley
explained that the team screened for a variety of chemical analogs to a
“small-molecule known to inhibit the ALDH1A family of enzymes.”
“From
these experiments, we identified 673A, a potent inhibitor of the ALDH1A
family,” says Grimley. Then, the researchers showed that this drug
efficiently killed cancer stem-like cells in ovarian cancer cell lines.
“Since
[cancer stem-like cells] have been implicated in chemotherapy resistance, we
investigated the effects of 673A in combination with cisplatin [a chemotherapy
drug] in chemotherapy-resistant cells.”
“We
found that, as a single agent, 673A had only a slight effect on these
cells,” the co-author told MNT. However, in combination with the chemo
drug, it was highly effective.
The
researchers also treated chemoresistant cancer cells with the drug, injected
them into mice, and monitored the growth of the tumor for 28 days.
“Although
the cisplatin-treated cells produced tumors similar in size to those produced
by untreated cells, 673A-treated cells produced tumors that were 4–5-fold
smaller,” reports Grimley.
Finally,
Dr. Buckanovich and team injected chemoresistant ovarian cancer cells in
rodents. Then, they treated one group of mice with chemo alone and another
group with chemo in conjunction with 673A.
The
researchers monitored the mice for 6 months. When 673A was used together with
chemotherapy, the tumors in almost two-thirds of the mice were in remission
after 6 months. By contrast, all of the rodents that received just chemo died.
Also,
Dr. Buckanovich explains that, in conjunction with chemotherapy, 673A was 10
times more effective at annihilating stem-like cells than previous ALDH
inhibitors.
“It’s
like one plus one equals 10,” Dr. Buckanovich comments. “That was
really striking to me, how synergistic the two drugs were. That’s important
because it means you can potentially use lower doses and reduce toxicity for
patients.”
New drug may improve survival rates
Study
co-author Grimley commented on the significance of the findings for MNT.
“Given all that we knew about the importance of ALDH1A enzymes in
chemotherapy resistance,” he said, “disease recurrence, and their
link to [cancer stem-like cells], our hypothesis was that targeting the ALDH1A
family would be an excellent therapeutic approach and this study certainly
helps to validate that hypothesis.”
“Treatment
options and cure rates for epithelial ovarian cancer have been stagnant for the
past 3 decades,” said Grimley.
“Given
the high frequency of recurrence and chemoresistant disease, drugs like 673A
have the potential to significantly improve ovarian cancer survival
rates.”
Edward Grimley
However,
the authors also caution that the drug needs more work before it reaches the
market. The drug is not yet as soluble as it should be, and it doesn’t last
very long in the body. Also, scientists have not tested it in humans.
SOURCE: MEDICAL NEWS TODAY
Kayode Ojo
Kayode Emmanuel Ojo is the Co-Founder and Managing Director at SHEFFA Limited. He is presently studying Computer Science at the National Open University, Victoria Island, Lagos.