Potent in vivo antineoplastic activity of MCR peptides MCR-4 and MCR-14 against chemotherapy-resistant human small cell lung cancer.

Previous studies have shown that MCR peptides possessing the retinoblastoma protein (RB) fragment LFYKKV as the active site are able to inhibit the proliferation of human non-small cell lung cancer (NSCLC) cells in vitro and in vivo. The goal of the present study was to test these compounds against human small cell lung cancer (SCLC) in vivo since this tumor is notoriously resistant to conventional therapy or, respectively, is characterized by rapid relapse after initially successful treatment. We herein report that the MCR peptides MCR-4 and MCR-14 display potent antiproliferative activity against RB-negative H82 SCLC xenograft tumors in nude mice, whereas the chemotherapeutic agent VP-16 tested in parallel in a clinically relevant dose had no anti-tumor effect. These encouraging results warrant accelerating the introduction of MCR peptides into clinical trials in patients with RB-negative tumors such as SCLC in the near future.