A UTHealth Houston-led team has identified a promising new avenue to curb the growth and spread of tumors associated with hard-to-treat lung and other cancers.
The research was published today in the Proceedings of the National Academy of Sciences and led by Xiaochao Tan, PhD , assistant professor in the Department of Integrative Biology and Pharmacology at McGovern Medical School at UTHealth Houston.
The team’s findings build on their efforts to better understand the role of the Golgi apparatus in a specific subtype of non-small cell lung cancer, the most common type of lung cancer that is often diagnosed after it has spread to other parts of the body.
“The therapeutic options for this type of lung cancer are minimal. In this study, we were able to identify a weak point in this type of lung cancer,” Tan said.
The Golgi apparatus is the part of the cell that modifies, sorts, and packages proteins for delivery to other parts of the cell or for secretion outside the cell. Tan’s previous work found that lung cancer cells have extra copies of an abnormal piece of DNA known as chromosome 3q, which encodes several proteins associated with the Golgi apparatus.
The current work identified a region of chromosome 3q that contains the gene encoding an enzyme Phospholipase D1, or PLD1. Researchers found that lung cancer cells produce unusually high levels of PLD1, and—through the Golgi apparatus—send cancer-promoting materials out of the cell, allowing tumors to grow and survive.
Using mouse models, the team discovered that these cancer cells could be targeted using a drug delivered directly to the cell that curbs its reliance on PLD1. The drug significantly slowed the growth of the tumors in mice without causing any other negative health effects.
The results indicate that targeting the Golgi secretory machinery is a promising treatment option for multiple types of cancer.
“Extra copies of chromosome 3q are common in cancers such as head and neck cancer and esophageal cancer. Therefore, patients with these cancers may also benefit from this treatment,” Tan said.
Authors from UTHealth Houston include Shike Wang, PhD; Guangwei Du, PhD; Sieun Lee, PhD; and Dakai Zhang, PhD.
Other authors include: Guan-Yu Xiao, PhD of the University of Kentucky; Derrick L. Cardin, PhD, and Yuting Xu, MS, of Tulane University School of Medicine; Chao Wu, PhD, and Biyao Zhou, PhD, of The University of Texas MD Anderson Cancer Center; and William K. Russell, PhD, of The University of Texas Medical Branch.
Proceedings of the National Academy of Sciences