Uproleselan Targets E-Selectin Biomarkers in AML

Biomarkers represent characteristics of the body that can be measured. They are found in the blood and tissues and can signal the presence of disease. Biomarkers are used to determine targeted mutations, genetic lesions and chromosomal abnormalities and can help explain how they affect a patient and their cancer.

E-selectin is a biomarker that is currently being investigated for its efficacy in AML treatment.

According to Brian Jonas, MD, at UC Davis Health,

“E-selectin is involved in the bone marrow microenvironment where the hematopoietic stem cells, and the leukemia stem cells are located. It's a molecule, it's kind of like a sticky molecule that binds the selected ligand on the cell, and then it causes them to be retained or stay in that microenvironment.” This can promote the growth and survival of cancer cells in the bloodstream.

Uproleselan (also known as GSI-1271) is a new drug that targets e-selectin molecules. It disrupts the cell survival pathways, enhances chemotherapy response and can improve survival. In a completed phase 1/2 trial, uproleselan led to high rates of remission and low rates of mucositis in patients with relapsed/refractory AML. “Investigators sought to evaluate the safety, tolerability, and antileukemic activity of uproleselan at 5-20 mg/kg with mitoxantrone, etoposide, and cytarabine (MEC) in patients with relapsed/refractory AML.”

75% of patients receiving uproleselan in this trial had prior remission of less than 1 year and 50% of patients had unfavorable cytogenetics (changes in chromosomes).

• 91 patients were studied
• Median age of patients was 59
• Overall survival (OS) for relapsed or refractory patients was 8.8 months
• Overall survival in newly diagnosed patients was 12.6 months

“Treatment with the e-selectin inhibitor was associated with higher rates of response and improved survival in patients with relapsed/refractory disease. Treatment in the study was also well-tolerated.” 67% of patients had received one previous treatment and 33% had received two or more. 12 patients had already received a stem cell transplant.

A newer, recruiting trial is testing uproleselan in combination with azacitidine and venetoclax. “Uproleselan may help block the formation of growths that may become cancer. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving uproleselan with azacitidine and venetoclax may help kill more cancer cells.”

To learn more about this open clinical trial, visit HealthTree's

Clinical Trial Finder