Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors.

ABSTRACT:

Background

Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease.

Methods

We investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients. Mechanistic studies were performed to assess co-localization

SUBMITTER: Turner JG 

PROVIDER: S-EPMC4997728 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature