RT Journal Article
SR Electronic
T1 The Preclinical Activity of Lenalidomide in Indolent Urothelial Carcinoma
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3383
OP 3389
VO 34
IS 7
A1 JIAN, WEIGUO
A1 LEVITT, JONATHAN M.
A1 LERNER, SETH P.
A1 SONPAVDE, GURU
YR 2014
UL http://ar.iiarjournals.org/content/34/7/3383.abstract
AB Background: Lenalidomide is an IMiD® immunomodulatory drug, which may warrant evaluation in urothelial carcinoma (UC). Materials and Methods: The in vitro and in vivo activity of lenalidomide was evaluated in human and murine UC cell lines. Tumors were evaluated by immunohistochemistry for (CD31), cleaved caspase-3 (CC3) and CD3+/CD20+ lymphocyte infiltration. Cereblon, a molecular target of lenalidomide was analyzed by immunohistochemistry. Results: Significant pro-apoptotic activity, and reduction of cell viability was seen at low micromolar concentrations of lenalidomide against indolent human RT4 UC cells in vitro. Cereblon expression was quantitatively lower in sensitive RT4 cells compared to resistant 5637 cells. In RT4 xenografts, lenalidomide significantly reduced tumor size and CD31 expression, and increased expression of CC3 (p<0.05). Cereblon expression increased in lenalidomide-treated RT4 xenografts (p<0.05). Conclusion: Lenalidomide demonstrated preclinical activity against superficially-invasive low-grade UC cells attributable to direct tumor cell apoptosis and anti-angiogenic activity. Clinical trials are warranted in patients with indolent UC.