Hawaiian scientists find new molecular target for mesothelioma treatmentsIn the ongoing search for new angles from which to attack mesothelioma, researchers at the University of Hawaii may have found something promising. The institute's cancer biologists - together with scientists from New York and Italy - recently announced that a protein linked to malignant pleural mesothelioma (MPM), other cancer and inflammation may be a novel target for chemotherapy.
Their full findings appeared in the journal Cancer Research.
HMGB1: Part of the inflammation cascade
The protein, called high-mobility group box 1 (HMGB1) is not a new discovery. It has been studied since the 1970s as a chromosomal protein that helps with DNA transcription, replication and repair.
It also plays a role in inflammation. Certain white blood cells secrete HMGB1 as part of the inflammatory response to infections or cancers. For this reason, scientists have paid increasing attention to the presence of HMGB1 in the rise of malignancies like mesothelioma.
Now, led by the University of Hawaii group, an international team of authors has implicated HMGB1 in the genesis of MPM. The mechanism, as always, appears to be inflammation.
Cell damage? Look to asbestos
Researchers identified HMGB1 as a potential target for therapies because, as the Honolulu Star-Advertiser described it, this protein is part of a"damage-associated molecular pattern." What could cause enough cellular injury to lead to dangerous inflammation and, ultimately, mesothelioma? The likely culprit is asbestos exposure.
The fireproof mineral and infamous carcinogen is currently the only proven cause of MPM. In the new study, researchers found that when cellular damage leads to mesothelioma, HMGB1 is associated with the transformation of health mesothelial cells into malignant tumors.
"HMGB1 establishes an autocrine circuit in MPM cells that influences their proliferation and survival," the team explained of their findings. "MPM cells strongly expressed HMGB1 and secreted it at high levels in vitro. Accordingly, HMGB1 levels in MPM patient sera were higher than that found in healthy individuals."
What does this mean for mesothelioma patients?
There are at least three potential applications for HMGB1. The first is to use it as a yardstick for MPM's severity. By performing blood tests that measure HMGB1 levels, doctors might be able to gauge the extent of the disease. The second is as an early diagnostic tool, though researchers said more work needs to be done to confirm this possibility.
And the third? Evidently, HMGB1 is a promising target for chemo. The team found that, in mice grafted with human MPM tumors, the chemical suppression of HMGB1 slowed the growth of mesothelioma tumors and extended average lifespan.
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