Targeting the Pim kinases in multiple myeloma
Multiple myeloma (MM) is a type of plasma cell cancer that remains challenging to cure, highlighting the urgent need for new treatment strategies to improve patient survival. The PIM kinases, a small family of serine/threonine kinases, are increasingly expressed in hematological malignancies. Among them, Pim-2 is particularly prominent in MM and represents a promising therapeutic target. Pim-2 is upregulated by the bone marrow microenvironment, where it facilitates tumor cell proliferation and survival. Additionally, Pim-2 plays a critical role in the bone damage commonly associated with MM. Other potential roles of Pim kinases in MM include aiding the trafficking of malignant cells, enhancing oncogenic signaling in the hypoxic bone marrow, and contributing to therapy resistance. Several Pim inhibitors are currently under development, with lead compounds progressing to clinical trials. Notably, the ATP-competitive Pim inhibitor LGH447 has recently demonstrated activity as a single agent in MM. It is expected that Pim inhibition will offer clinical benefits, particularly when combined with standard treatments and/or novel therapies targeting other survival pathways in MM.