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Innovative research sheds light on how lung cancer advances

Funding by the Department of Defense could ultimately help drive research that underpins better treatments for cancer.

Asst. Prof. Huanhuan Joyce Chen at the UChicago Pritzker School of Molecular Engineering is peering deep into the genetic mutations of pulmonary carcinoids — a cancer type with the predominant cell of origin of pulmonary neuroendocrine cells.

Though a rare form of lung cancer — only about two percent of lung cancer cases are pulmonary carcinoids — these tumors generally only have one treatment option: surgery.

With most tumors, surgery is enough to cure the patient. But if pulmonary carcinoid becomes atypical and therefore more aggressive, patients have no further treatment options. To develop new treatments for these tumors, scientists need to better understand which of these mutations drives the cancer.

Chen is compelled to find answers, and has received a new Department of Defense grant to support her work. The three-year, $574,000 Rare Cancers Research Program Idea Development Award will fund Chen’s work, which aims to understand cancer-driving mutations.

In a review of the scientific literature, Chen found that genetic sequencing of pulmonary carcinoids had unearthed 38 high-frequency mutations. The usual process for finding such mutations is to take the carcinoid cell lines, knock down these mutations one by one, and see which are “drivers” of cancer and which are just “passengers.” But pulmonary carcinoids tissue is difficult to obtain. Often, the cancerous cells change characteristics when grown in a culture.

Chen’s previous work used human induced pluripotent stem cells to create pulmonary neuroendocrine cells — the types of cells where pulmonary carcinoids originate. In fact, they were the first team capable of generating these lung cells from stem cells.

Armed with the grant, she and her team will introduce genetic alterations to these cells to observe their cancer transformation and better understand which genetic abnormalities feed cancer.

“The hope is that this information could then serve to help create novel therapeutics that could help the patients who don’t have any therapeutic options,” Chen said.

And because several lung cancers originate in pulmonary neuroendocrine cells — including small cell lung carcinoma, an aggressive disease with a poor prognosis — the work could also provide a window into the mechanisms of that cancer.

“We hope to extend this work to several lung cancers to further test drivers and hopefully create a path for more therapeutic options,” she added.