In a pre-clinical study led by UCLA, scientists discovered that treating a subset of multiple myeloma tumors with therapeutic drugs has the potential to prevent them from progressing.
Published online in Cancer Research, the study analyzed a subtype of human multiple myeloma cells that express the Hexokinase enzyme known as HK2 but do not express the Hexokinase enzyme isoform HK1. The majority of human multiple myeloma cells, and many other cancers, express both of these hexokinase enzymes. Scientists were able to use a triple-combination therapy to prevent the multiple myeloma tumors that do not express HK1 from progressing. The triple therapy combination included an oxidative phosphorylation inhibitor metformin, a fatty acid oxidation inhibitor perhexiline and an antisense oligonucleotide that specifically suppresses the expression of the HK2 enzyme.
“This study builds on earlier studies where we identified a common property that is shared by subsets of tumors, regardless of their cell or tissue of origin, and formulated a way to treat them,” said Dr. Harvey Herschman, a member of the UCLA Jonsson Comprehensive Cancer Center. “This common characteristic was not previously recognized. Now that we’ve identified this common property, it should be feasible to use a common therapy to target and fight multiple cancers, including multiple myeloma, originating from many different organs.”
The earlier research by UCLA scientists demonstrated that there exists in all cancer types a subclass of tumors that have the common biological characteristic of expressing HK2, but not HK1. In a subsequent study, the scientists developed the therapeutic approach to treat this subclass of tumors by targeting a primary type of liver cancer called hepatocellular carcinomas. The new study supports for the first time the possibility of clinical development of the triple combination therapy as a treatment for HK1 null, HK2 positive multiple myeloma.
The team that contributed to this study includes lead author Shili Xu; and Hanna Doh, Ryan Trinh, Art Catapang, Jason Lee, Daniel Braas, Nicholas Bayley, Reiko Yamada, Alex Vasuthasawat, Joshua Sasine, John Timmerman, Sarah Larson, Youngsoo Kim, Robert MacLeod, Tianyuan Zhou, Sherie Morrison and Harvey Herschman; all of UCLA. Robert MacLeod and Tianyuan Zhou are employees of Ionis Pharmaceuticals.
