Researchers discover distinct pathways in lung adenocarcinoma

Volume 8, Issue 4, December 2019

Summary

Study results may help investigators predict how cancer subtypes will respond to targeted therapies.

Alan P. Fields, Ph.D.

Alan P. Fields, Ph.D.

Researchers on Mayo Clinic's Florida campus can now distinguish between two pathways where lung adenocarcinoma can develop, a discovery that could help future patients. The findings were published in August 2019 in the journal Cancer Cell.

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.

"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," said Alan P. Fields, Ph.D., a cancer biologist at Mayo Clinic in Florida and the published study's senior author. Dr. Fields is also the Monica Flynn Jacoby Professor of Cancer Research at Mayo Clinic.

Dr. Fields 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 called 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.

Once these two pathways were revealed in mice, Dr. Fields and his colleagues considered how their discovery could apply to people. To begin, they compared the pathways in the mouse model to the six known molecular subtypes of lung adenocarcinoma in people. 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.

To 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 that investigators can predict how these cancer subtypes will respond to targeted therapies.

As a next step, the team is working to determine whether it can effectively and specifically identify PKCiota-dependent versus independent lung adenocarcinoma in people and confirm whether experimental drugs can predictably inhibit the growth of lung cancer in patients with the PKCiota-dependent and independent types.

Because the PKCiota pathway is also important to other cancers, the researchers think that their findings may apply beyond lung cancer.

This work builds on previous efforts by Dr. Fields and his colleagues, who were the first to discover the connection between PKCiota and the initiation, promotion and spread of lung cancers.

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