Potential involvement of protein phosphatase 2A in temsirolimus-mediated resensitization to cetuximab in colon cancer cells

Excerpt

We read with great interest the work recently published by Wang et al. (2014) which provides experimental evidences about the synergistic effects of temsirolimus with cetuximab via down-regulation of cancerous inhibitor of protein phosphatase 2A (PP2A) (CIP2A) in colorectal cancer (CRC) cells. CIP2A is, as indicated by its own name, a potent endogenous PP2A inhibitor frequently deregulated in human cancer (Junttila et al. 2007). The authors found that temsirolimus, an inhibitor of the mammalian target of rapamycin (Hudes et al. 2007), downregulates CIP2A by decreasing its transcriptional levels and enhancing protein degradation through the lysosomal autophagy pathway. Moreover, they observed that temsirolimus was able to sensitize the K-ras codon 13 mutated HCT-15 cell line to cetuximab in a mouse model. These are important findings since the development of resistance to cetuximab in patients with metastatic CRC is a very recurrent event after few months of treatment that severely compromises their clinical outcome. Therefore, it would be very interesting to develop alternative therapeutic strategies that could resensitize CRC cells to cetuximab, then enhancing the period of time in which this drug is effective. …