Plixorafenib simultaneously inhibits the activity of several key pathways in cutaneous squamous cell carcinoma.

Plixorafenib, a new drug developed for treating melanoma and lung cancer, may also stop the progression of cutaneous squamous cell carcinoma, new research suggests.

Researchers out of the University of Turku, Finland, discovered that plixorafenib (also called PLX8394) simultaneously inhibits the activity of several key pathways in cutaneous squamous cell carcinoma.

“Plixorafenib was originally developed to treat melanoma and lung cancer caused by a specific mutation and it is currently in phase 2 clinical trials for these two cancers. However, we noticed that this new drug targets multiple signaling pathways in cutaneous squamous cell carcinoma. This can be achieved with doses that seem to have no significant side effects,” says Jyrki Heino, a Professor of Biochemistry of the University of Turku in Finland, in a news release.

The first author of the article, Senior Research Fellow Elina Siljamäki, used 3D cell culture models that mimicked cutaneous squamous cell carcinoma tumors in laboratory conditions.

“In our earlier studies, we have observed that two signaling proteins in the cell, transforming growth factor-β (TGF-β) and Ras proto-oncoprotein, play a key role in the spread of cutaneous squamous cell carcinoma. In this study, we showed that plixorafenib, which was developed to inhibit the Ras signaling pathway, also blocked the activation of the TGF-b pathway and the growth of human cutaneous squamous cell carcinoma in mouse models,” explains Siljamäki.

The discovery shows that a single drug can inhibit several different cancer-causing proteins or overly active signaling pathways and therefore slow down the spread of cancer.

In addition, the study showed that drugs that have progressed to clinical trials can have a broader set of targets and therefore be used more widely. As the safety of the drug has already been proven, it can be introduced more quickly to treat new patients.

“Our results show that plixorafenib is a very promising candidate for a clinical trial for treating local or metastatic cutaneous squamous cell carcinoma,” Veli-Matti Kähäri, a Professor of Dermatiology at the University of Turku.

The study appears in Oncogene.

PHOTO CAPTION: The red dots in the picture are dyed cancer cells. The bottom row treated with Plixorafenib (PLX8394) shows that the drug significantly inhibits the invasion of cancer cells in the collagen gel. In the upper row, the control cells are moving without inhibition. The movement of the cells was followed with a confocal microscope for five days. Scale bar 500 μm.

PHOTO CREDIT: Elina Siljamäki