The study provides important new detail on how metastasis from breast
cancer can lead to relapse, even if the primary cancer is in remission.
The research highlights a possible new application of GMI-1271,
currently in a Phase 1/2 clinical trial in AML, as a potential treatment
for solid tumors. Data from the study also suggest a possible
therapeutic avenue to test GMI-1359, a
"The preclinical data published in an important peer-reviewed journal
demonstrate key roles for both E-selectin and CXCR4 in progression of
metastatic breast cancer," said
The researchers found that breast cancer cells accumulate in regions of the protective bone marrow, an environment rich in E-selectin and SDF-1 (which binds to CXCR4, another molecule associated with cancer cell adhesion and proliferation). GMI-1271, by inhibiting E-selectin, blocks trafficking of breast cancer cells into bone marrow regions where metastasis can become dormant and protected from chemotherapy treatment. At the same time, researchers found that inhibition of CXCR4 as well as of E-selectin could mobilize and excise dormant metastasis from these protective niches and block their reentry, thereby potentially eliminating a common site for metastases and source of relapsed disease. These effects indicate a potential role in treatment of breast cancer not only for GMI-1271, but also for GMI-1359, which inhibits the actions of both E-selectin and CXCR4.
GMI-1271 is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with AML cells as a targeted approach to disrupting well-established mechanisms of leukemic cell drug resistance within the bone marrow microenvironment. Preclinical research points to the drug's potential role in moving cancerous cells out of the protective environment of the bone marrow where they hide and escape the effects of chemotherapy. In preclinical studies using animal models of AML, the results of which were presented at meetings of the American Society of Hematology (ASH), GMI-1271 was also associated with a reduction of chemotherapy-induced neutropenia and chemotherapy-induced mucositis.
is a compound that targets both E-selectin and CXCR4, which aid in
cancer cell resistance to chemotherapy. The compound is in preclinical
evaluation. GMI-1359 is a potent dual antagonist of both E-selectin and
CXCR4, demonstrating anti-tumor activity in preclinical models of
pancreatic cancer, FLT-3+ acute myeloid leukemia (AML), and prostate
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements regarding the
clinical development plans for GMI-1271 and GMI-1359 and potential
treatment indications for these drug candidates. Actual results may
differ materially from those in these forward-looking statements. For a
further description of the risks associated with these statements, as
well as other risks facing
News Provided by Acquire Media