Targeted Therapy Enhances Chemotherapy, Improves Outcomes in Retinoblastoma
The effectiveness of chemotherapy was enhanced by targeting survivin, a protein that inhibits apoptosis or cell death, according to preclinical research in cells and mouse models of retinoblastoma (Rb).1
Retinoblastoma is the most common malignant tumor of the eye in children. This study demonstrates for the first time that combining YM155, which targets survivin, and chemotherapy provides a therapeutic advantage for Rb cells and tumors.
Most therapy for retinoblastoma includes chemotherapy agents such as carboplatin and topotecan. The researchers examined whether such agents induced a prosurvival phenotype associated with increased expression of survivin in Rb cells and Rb tumors growing in mouse models.
Exposure to chemotherapy resulted in elevated levels of survivin in 2 human Rb cells lines but not in normal ocular retinal pigmented epithelial cells. Also, the level of survivin in the Rb cells was affected by YM155 but in the normal cells. Combining YM155 and chemotherapy was more effective in enhancing Rb cell death than using either alone.
The combination was tested in Rb tumors growing in mouse eyes, and the same positive results occurred when YM155 was combined with carboplatin.
"Our study shows proof of concept, that we can enhance chemotherapeutic approaches to retinoblastoma while using the same dosage," said Charles Gomer, PhD, of the Children's Center for Cancer and Blood Diseases at Children's Hospital of Los Angeles in California. "We're hopeful that following additional preclinical studies that this combination therapy will offer better outcomes to children with retinoblastoma and perhaps the possibility of reduced chemotherapy, reducing long-term adverse effects."
1. Ferrario A, Luna M, Rucker N, et al. Targeting survivin enhances chemosensitivity in retinoblastoma cells and orthotopic tumors. PLOS ONE, 2016;11(4):e0153011. doi:10.1371/journal.pone.0153011.