In the world of experimental, targeted mesothelioma treatments, scientists have thousands of potential targets to work with. Literally – since, according to Shayne Cox Gad’s Handbook of Pharmaceutical Biotechnology, the human body contains at least 3,000 unique enzymes and 40,000 discrete proteins. While some of these molecules have nothing to do with malignant growth, others have been tied to the genesis of specific cancers.
CK2-alpha is one such enzyme. In a landmark study published in the journal PLoS ONE, researchers from the Thoracic Oncology Laboratory at the University of California, San Francisco (UCSF) became the first team to link CK2-alpha to a cellular signalling pathway that can cause respiratory cancers if uncontrolled.
This knowledge may contribute to better treatments for malignant pleural mesothelioma (MPM).
The first domino to fall
According to the report, CK2-alpha is responsible for “switching on” at least 300 separate proteins in the human body. Hence, this enzyme is so important for the delicate balance of cell growth and death that (researchers reasoned) CK2-alpha could easily lead to cancers if it went haywire.
The team explained that, in a number of malignancies, CK2-alpha levels are higher than normal. In fact, cancers that have very high CK2-alpha concentrations often have poorer prognoses.
Why? Well, without being sure, a number of oncologists have suspected that this enzyme can set off a cascade of cellular effects that cause uncontrolled growth.
To do so, overactive CK2-alpha seems to work through the Hedgehog (Hh) family of proteins – namely, the Indian, Desert and Sonic Hedgehog trio. (And yes, the latter is named for a video game character.) Hh proteins control organ development and stem cell growth. When CK2-alpha levels jump – possibly due to asbestos exposure – the enzyme probably cranks up the activity of the Hh proteins, leading to the creation of cancerous stem cells.
At least, that was the theory. Now, the UCSF team has essentially proved it.
Establishing it three separate ways
In cementing CK2-alpha’s role as an Hh destabilizer and respiratory cancer generator, the group went about it in three distinct ways:
- They analyzed 100 separate cancer tissues and established that the levels of CK2-alpha often match those of Gli1, a protein that, to put it crudely, does the Hh proteins’ dirty work.
- The team used chemicals to shut off CK2-alpha activity in cancer cells. This resulted in lower levels of Gli1. It also led to lower levels of cancer stem cells in the tissue.
- The UCSF group tried the opposite, cranking up CK2-alpha production. This led, as they suspected, to an overabundance of Gli1.
Researchers concluded that CK2-alpha may be a novel target for respiratory cancer treatments.