Thalidomide, lenalidomide and pomalidomide reduce the metastatic capability of cancer cells in vivo and in vitro

1173 Thalidomide (Thalomid®), lenalidomide (Revlimid®, CC-5013) and pomalidomide (CC-4047), display immunomodulatory, anti-angiogenic and anti-apoptotic effects, although little is known about the primary mode of therapeutic action in patients with cancer. Thalidomide is FDA approved, in combination with dexamethasone, for the treatment of newly diagnosed multiple myeloma (MM) patients. Lenalidomide is FDA approved in combination with dexamethasone for the treatment of MM patients who have received at least one prior therapy. Pomalidomide is being investigated as an anticancer agent in clinical trials. As part of a continuing research effort, we have investigated the effects of these agents on the metastatic capacity of a murine colorectal cell line in vivo and in vitro. The effects of these agents on the metastatic capacity of CT26 cells were established using a number of models. Results indicated that all three drugs significantly inhibited the metastatic capability of CT26 cells. Anchorage-independent growth was significantly reduced, as was migratory capacity and invasive competence (Table). In addition, an in vivo metastasis model was used whereby CT26 cells were administered by IV into the tail vein of BALB/c mice (n=15) at ten-weeks of age, and allowed to develop spontaneous metastases within the lungs. Mice challenged IP with pomalidomide (50 mg/kg) presented with a significantly lower number of metastatic pulmonary nodules relative to control mice injected with DMSO (50.8% ± 6.6% vs. 100.0% ± 10.1% at day 14; p