CRM1 as a new therapeutic target for non-Hodgkin lymphoma

• The CRM1 may serve as a novel target for NHL therapy.
• KPT-SINEs are highly potent in vitro and in vivo in NHL.
• KPT-SINEs are promising clinical candidates for NHL treatment.

The chromosomal region maintenance 1 (CRM1) may serve as a novel target for cancer treatment. Here, we investigated the anti non-Hodgkin lymphoma (NHL) activity of two novel CRM1 inhibitors (KPT-185 and KPT-276) in vitro and in vivo. KPT-185 displayed potent antiproliferative properties and induced cell-cycle arrest and apoptosis in several NHL cell lines and patients’ tumor cells. The antitumor activity mainly consisted of inducing caspase cleavage and downregulating the expression of antiapoptotic proteins such as CRM1, nuclear factor-κB, and survivin. Furthermore, oral administration of KPT-276 significantly suppressed tumor growth in mice with Jeko-1 xenograft without any major toxic effects.