Cancers, Vol. 13, Pages 335: Targeting E-Selectin to Tackle Cancer Using Uproleselan

Cancers, Vol. 13, Pages 335: Targeting E-Selectin to Tackle Cancer Using Uproleselan Cancers doi: 10.3390/cancers13020335 Authors: Barbara Muz Anas Abdelghafer Matea Markovic Jessica Yavner Anupama Melam Noha Nabil Salama Abdel Kareem Azab E-selectin is a vascular adhesion molecule expressed mainly on endothelium, and its primary role is to facilitate leukocyte cell trafficking by recognizing ligand surface proteins. E-selectin gained a new role since it was demonstrated to be involved in cancer cell trafficking, stem-like properties and therapy resistance. Therefore, being expressed in the tumor microenvironment, E-selectin can potentially be used to eradicate cancer. Uproleselan (also known as GMI-1271), a specific E-selectin antagonist, has been tested on leukemia, myeloma, pancreatic, colon and breast cancer cells, most of which involve the bone marrow as a primary or as a metastatic tumor site. This novel therapy disrupts the tumor microenvironment by affecting the two main steps of metastasis—extravasation and adhesion—thus blocking E-selectin reduces tumor dissemination. Additionally, uproleselan mobilized cancer cells from the protective vascular niche into the circulation, making them more susceptible to chemotherapy. Several preclinical and clinical studies summarized herein demonstrate that uproleselan has favorable safety and pharmacokinetics and is a tumor microenvironment-disrupting agent that improves the efficacy...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research