Scientists at the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), recently identified a new biomarker to predict sensitivity to rapamycin, an immunosuppressive agent that has shown promise as a cancer therapeutic and approved for clinical application; but patients’ response to this class of drugs is often unpredictable.
The knowledge gained may help develop better treatment strategy for colorectal cancer. The study found that a gene, PPP2R2B, is lost in colorectal cancer and this loss results in the activation of the PDK1-Myc signalling, an important cancer pathway leading to rapamycin resistance.
In addition, it was shown that the combination of rapamycin and PDKI inhibitor overcomes rapamycin resistance, which might prove useful for the treatment of colorectal cancer.
Led by GIS Group Leader Dr Yu Qiang, the finding was published in the 16 November 2010 print issue of Cancer Cell.
“This study is the first of its kind to provide clinical evidence pointing to a wide occurrence of PP2A tumor suppressor inactivation in colorectal cancer, which has not been previously shown,” said Dr Yu Qiang.
“Our data demonstrate that one of the PP2A genes, PPP2R2B, is epigenetically inactivated in colorectal cancer. Thus, PPP2R2B is likely to be a useful biomarker to predict rapamycin sensitivity. This study reflects our focus on addressing clinically relevant questions and generating knowledge that may meet industry interests”.
Professor David Virshup, Program Director for Cancer and Stem Cell Biology at Duke-NUS Graduate Medical School added, “While we have long suspected a major role for PP2A in human cancers, mutations in these genes are rare. Dr. Yu’s careful studies confirm our suspicions and tell us how these PP2A genes are altered in cancer.
Importantly, his work also provides new insights into better ways to treat cancers. This is yet another example of how strong basic science can combine with medical science to make advances that can make a difference.”
Source: Agency for Science, Technology and Research (A*STAR)
Genome Institute of Singapore