Discovery of distinct lung cancer pathways may lead to more targeted treatments
Fla. — Known for its poor prognosis, lung adenocarcinoma is the most common
type of lung
cancer, responsible for about 4 of 10 diagnoses, according to the
National Cancer Institute. Researchers on Mayo
Clinic’s Florida campus can now distinguish between two pathways
where this deadly cancer can develop. They say their discovery could help
future patients. The findings appear in Cancer
“The ability to identify the specific pathway by which a patient’s lung adenocarcinoma came about increases our ability to predict which patients are likely — or unlikely — to benefit from a particular treatment, and hopefully offer alternative options to patients whose cancer subtype is unlikely to respond,” says Alan Fields, Ph.D., a cancer biologist and the study’s senior author. Dr. Fields is the Monica Flynn Jacoby Professor of Cancer Research at Mayo Clinic.
and his team studied the molecular features of lung adenocarcinoma in mice and
found two ways that this cancer can develop. The first way depends on the
cancer-causing gene known as “protein kinase C iota (PKCiota).” The second
pathway, identified as the “Wnt/Beta-catenin signaling pathway,” was found
to operate independently of PKCiota. Lung adenocarcinomas that stem from the two
different pathways were also found to form in different regions of the lung and
through different cells of origin.
these two pathways were revealed in mice, Dr. Fields and colleagues considered
how their discovery may apply to people. To begin, they compared the pathways
in the mouse model to the six known molecular subtypes of this cancer in
humans. The scientists found a match: a molecular marker that allowed them to
predict which human lung adenocarcinoma cells originated from the PKCiota-independent
pathway that they’d discovered in mice.
test whether the tumors arising from the PKCiota-dependent and independent pathways
might be sensitive to specific cancer therapies, Dr. Fields’ team then conducted
an experiment on human cells and the mouse model. As hypothesized, they found
that two drugs affected the adenocarcinoma subtypes differently, depending on
their underlying pathway. These results suggested to the investigators that they
can predict how these cancer subtypes will respond to targeted therapies.
a next step, the team will work to determine whether they can effectively and
specifically identify PKCiota-dependent versus independent lung adenocarcinoma
in human patients and confirm whether experimental drugs can predictably inhibit
the growth of lung cancer in the PKCiota-dependent and independent patients.
Because the PKCiota pathway is also important to other cancers, the researchers think that their findings may apply beyond lung cancer.
work builds on previous efforts by Dr. Fields and colleagues, who were the first
to discover the connection between PKCiota,
the initiation, promotion and spread of lung cancers.
researchers are Ning Yin, Ph.D., the lead author of the study; Yi Liu, Ph.D.; Andras
Khoor, M.D., Ph.D.; Xue Wang, Ph.D.; E.
Aubrey Thompson, Ph.D.; Verline
Justilien, Ph.D.; Capella Weems; and Nicole
Murray, Ph.D. — all of Mayo Clinic — as well as Michael Leitges, Ph.D.,
of Memorial University of Newfoundland in Canada.
This study was supported by the National Institutes of Health, the Monica Flynn Jacoby Professor of Cancer Research endowment fund, a Mayo Clinic Center for Biomedical Discovery Career Development Award, and the Edward C. Kendall Fellowship in Biochemistry from the Mayo Clinic Graduate School of Biomedical Sciences. The authors report no conflicts of interest.
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Published at Thu, 01 Aug 2019 15:00:57 +0000