Blocking a cancer cell's shipping system slows tumors in mice

A cell's packing department is the target. In the lab of Xiaochao Tan, at McGovern Medical School at UTHealth Houston, the researchers looked at the Golgi apparatus, the structure that modifies, sorts and packages proteins before the cell sends them to other parts of its interior or outside it. Lung cancer cells, the team found, use this machinery to push out the materials that keep their tumors growing.

The starting point is a piece of DNA called chromosome 3q. Tan's earlier work showed that lung cancer cells carry extra copies of it, and that it encodes several proteins associated with the Golgi. The new study narrows the search to one region of that chromosome, the one containing the gene for the enzyme phospholipase D1, or PLD1. Lung cancer cells make unusually high levels of PLD1, and through the Golgi they send cancer-promoting material out of the cell. The tumors then grow and survive on that flow.

The team then tested whether that dependence could be exploited. In mouse models, a drug delivered directly to the cancer cells reduced their reliance on PLD1. The drug significantly slowed tumor growth in the mice, and the researchers reported no other negative health effects. The team describes this as a weak point in a cancer that has few options today, and the study is published in the Proceedings of the National Academy of Sciences.

For patients, the result is a possible new line of attack, not a treatment. The experiments were run in mice, and the study does not say when or whether the approach will be tested in people. Tan also points to a wider reach: extra copies of chromosome 3q are common in head and neck cancer and esophageal cancer, so patients with those diseases "may also benefit" if the approach holds up. That is a hypothesis drawn from the shared chromosome change, and it has not been tested in those cancers.

What changes, for now, is the map. If the Golgi secretory system is confirmed as a vulnerability across several cancers, researchers gain a shared target rather than a separate problem for each tumor type. The next steps the study points to are testing in other models and, eventually, clinical trials, though no date has been announced.