GMI-1359 is a small molecule that simultaneously targets E-selectin and CXCR4, two adhesion molecules — cell surface proteins that mediate the interaction between cells — that help cancer cells migrate and spread through the body.
“Our preclinical research in mice suggests that targeting E-selectin and CXCR4 with a single agent may potentially improve treatment of patients at risk of metastasis to bone, or whose tumors might have already spread,” Dorothy Sipkins, MD, PhD, one of the study’s lead investigators and a member of the Duke Cancer Institute, said in a press release.
Breast cancer can return, or relapse, in patients years after completing treatment, suggesting the existence of breast cancer cells that remain dormant. Sipkins and her team showed in a 2016 study that these dormant cells hide in protective sites — mostly in the bone marrow, where they are protected from chemotherapy effects — aided by CXCR4 and E-selectin.
Sipkins found that E-selectin allows breast cancer cells to enter the bone marrow, while CXCR4 anchors them to these protective environments, including the bone. The findings suggested that “combining a CXCR4 inhibitor to force the cells out of their niches and an E-selectin inhibitor to prevent metastasis to the bone marrow could help trap the cells in the vasculature [the blood vessels in an organ], where they could be killed with chemotherapy,” the researchers said.
“Her work reveals a potentially exciting approach to molecularly excise disseminated breast cancer cells with GMI-1359, which was rationally designed to inhibit both of these targets,” said John Magnani, PhD, GlycoMimetics’ senior vice president and chief scientific officer.
The upcoming study – expected to begin in the second half of 2019 – will examine the effects of multiple doses of GMI-1359 in breast cancer patients whose tumors have spread to the bone. The researchers’ goal is to determine the treatment’s safety, and identify the best dose and regimen for further trials.
“If ultimately shown safe and effective in clinical trials, this agent could represent a potentially novel approach to treating metastatic cancer, and we’re pleased to begin exploring the use of this investigational therapy in individuals with metastatic cancer,” said Kelly Marcom, MD, the trial’s co-lead investigator and also a member of the Duke Cancer Institute.
GlycoMimetics has already tested GMI-1359’s safety in a Phase 1 trial (NCT02931214), in which healthy adult volunteers were randomly selected to receive a single ascending dose of GMI-1359, or a placebo.