Study Shows Mesothelioma Growth Slowed by Blocking Specific Signaling Pathway
Stopping tumor growth and preventing metastasis in mesothelioma, which is highly aggressive and resistant to standard cancer treatments, is critical for increasing survival in patients. Now, researchers report that by intercepting a signaling pathway found in mesothelioma they can slow the growth of the insidious cancer.
Researchers from Korea found that by targeting and blocking the Hedgehog signaling pathway, responsible for signaling cells to grow, they could prevent the growth of “a more aggressive subpopulation of the cancer cells.” The researchers report that this side population of cancer cells are found in many lines of mesothelioma and are more aggressive cells with “stem cell features.”
Cancer stem cells, like normal adult stem cells, have the ability to self-renew. The cells can divide indefinitely leading to more cancer stem cells and child cells that can continue dividing ad infinitum. In a 2012 study from Singapore, researchers found that even though cancer stem cells make up just one percent of cancer cells, it is these cells that survive the effects of anti-cancer drugs and continue to grow and divide allowing the cancer to metastasize.
In the July 24 study, reported in Cancer Gene Therapy, the researchers targeted the cancer stem cells with the anticancer treatment cyclopamine, currently used in research only. Cyclopamine is a naturally occurring steroid alkaloid that inhibits the hedgehog pathway. They reported that the cyclopamine “significantly decreased the proliferation” of the mesothelioma cells by killing off cells and “shifting the cell cycle toward dormant phase.”
“The clonogenicity [the ability of a cell to form clones] and mobility of HMM [human malignant mesothelioma] cells were significantly decreased by cyclopamine treatment,” reported the study authors. “Treatment of HMM cells with cyclopamine significantly reduced the abundance of side population cells,” the authors added.
Citing statistics that mesothelioma, a pulmonary cancer caused by the inhalation of asbestos dust, is difficult to treat, and the cancer almost always recurs, the authors said, “studies on HMM carcinogenesis with new perspectives are urgently needed to improve the clinical outcome of HMM patients.”
The authors concluded:
“The present study showed that inhibition of hedgehog pathway markedly reduced the SP [side population] fraction in HMM cell lines, supporting the future clinical investigation of the hedgehog signaling as a novel target for HMM therapy, with the aim of increasing the efficacy while minimizing the toxicity of anticancer drugs.”
Mesothelioma is diagnosed in 3,000 Americans each year, with nearly the same number dying from the incurable cancer. New, effective treatments are desperately needed to improve survival and quality of life.
The study can be found in the July 24 issue of Cancer Gene Therapy.