Study Suggests Therapeutic Avenue for Transplant-Related Cancers

Results from a new study suggest that certain anti-angiogenic agents could be used to prevent or treat the cancers that occur in 15-20 percent of patients who receive an organ transplant. The study, which relied on laboratory and animal models, showed that a common and effective immunosuppressive agent used in organ transplant procedures increases the expression of vascular endothelial growth factor (VEGF), which is critical to a tumor's ability to develop blood vessels and recruit a blood supply. The study was published July 15 in Cancer Research.

"It may be that anti-VEGF agents given judiciously after transplantation can reduce future cancer occurrence," said the study's lead author, Dr. Soumitro Pal of the Transplantation Research Center at Children's Hospital Boston and Brigham and Women's Hospital. "We would need to figure out how to balance benefit and risk to keep cancer at bay."

Although there are several potential causes of cancer in patients following a transplant, the authors noted, this study focused on whether the drug cyclosporine could promote the growth of pre-existing "microtumors" in a mouse model of post-transplantation kidney cancer. First, however, they used kidney cancer cell lines to demonstrate that cyclosporine caused activation of the VEGF gene, that the extent of this activation was dose dependent, and that it increased expression of the VEGF protein. They found that cyclosporine also activates the intracellular signaling pathway PKC, which in turn increases the transcription of the VEGF gene.

Tumor growth was greater in mice given cyclosporine than untreated mice, they discovered. But simultaneously treating the mice with VEGF inhibitors slowed tumor growth. The authors noted that other studies have found pathways other than PKC via which cyclosporine could increase VEGF expression.