Underlying Pathway in Lung Cancer Could Identify Appropriate Targeted Treatments

Research has uncovered 2 pathways through which lung adenocarcinoma can develop, and that knowledge could help target treatments to patients who will benefit the most, according to a new study published in Cancer Cell.

According to the researchers, the first way lung adenocarcinoma can develop is through protein kinase C iota (PKCiota), a cancer-causing gene, and the second way is the Wnt/β-catenin signaling pathway, which operates independently of PKCiota.

"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," Alan Fields, PhD, the Monica Flynn Jacoby Professor of Cancer Research at Mayo Clinic and the study's senior author, said in a statement.

Fields and his team discovered the 2 pathways by studying the molecular features of lung adenocarcinoma in mice. They also discovered that the tumors arising from the pathways formed in different regions of the lung and through different cells of origin. They compared the pathways in the mice with 6 known molecular subtypes of the cancer in humans and they found a molecular marker that can predict which human lung adenocarcinoma cells originated from the PKCiota-independent pathway.

Next, the team tested whether tumors originating from the PKCiota-dependent and -independent pathways are sensitive to specific therapies by experimenting on human cells and the mouse model. They found that the pathway had an impact on how the drugs affected the tumor subtypes, which suggests they might be able to predict how cancer subtypes will respond to targeted therapies.

The PKCiota pathway is important in more cancer types than just lung adenocarcinoma, which means these findings could have implications beyond lung cancer.

Reference

Yin N, Liu Y, Khoor A, et al. Protein kinase Cι and Wnt/β-catenin signaling: alternative pathways to Kras/Trp53-driven lung adenocarcinoma [published online August 1, 2019]. Cancer Cell. doi: 10.1016/j.ccell.2019.07.002.