MELK (maternal embryonic leucine zipper kinase) signals cell division and may play a role in several kinds of cancer. In 2012, researchers screened for inhibitors of MELK and found a substance that they named OTSSP167. OTSSP167 shows promise as a chemotherapy drug.
Bone disease is a top cause of morbidity for multiple myeloma patients. Bone lesions cause bone pain, bone breakdown, and encourage further tumor growth. Even when chemotheraphy causes tumor remission, the bone lesions don’t heal. Bisphosphonates, the current standard of care, come with serious side effects.
Researchers Muller and Bolomsky investigated OTSSP167’s potential to treat multiple myeloma. In 2018, Bolomsky et al. found that OTSSP167 reduced tumor load in a multiple myeloma mouse model. As predicted, it worked by inhibiting MELK. The researchers also found that OTSSP167 reduced multiple myeloma bone disease, even at doses that were too low to inhibit tumor growth. They followed up on their findings in another 2018 paper.
In the follow-up, Muller et al. dosed bone cell cultures and multiple myeloma mice with OTSSP167. They found that OTSSP167 inhibits the growth and function of osteoclasts, cells that reabsorb bone, and stimulates osteoblasts, cells that produce bone. The mice dosed with OTSSP167 had fewer bone lesions and better bone volume than controls.
Muller et al. conclude that OTSSP167 has the potential to treat multiple myeloma tumors and to reduce bone lesions.
Chung S, Suzuki H, Miyamoto T, et al. Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer. Oncotarget. 2012 3(12):1629–1640. doi:10.18632/oncotarget.790
Muller J, Bolomsky A, Dubois S, Duray E, Stangelberger K, Plougonven E, Lejeune M, Léonard A, Marty C, Hempel U, Baron F, Beguin Y, Cohen-Solal M, Ludwig H, Heusschen R, Caers J. Maternal embryonic leucine zipper kinase inhibitor OTSSP167 has preclinical activity in multiple myeloma bone disease. Haematologica. 2018 Vol 103(8):1359-1368.
Bolomsky A, Heusschen R, Schlangen K, et al. Maternal embryonic leucine zipper kinase is a novel target for proliferation- associated high-risk myeloma. Haematologica. 2018 103(2):325-335.