TY - JOUR
T1 - Targeting e‐selectin to tackle cancer using uproleselan
AU - Muz, Barbara
AU - Abdelghafer, Anas
AU - Markovic, Matea
AU - Yavner, Jessica
AU - Melam, Anupama
AU - Salama, Noha Nabil
AU - Azab, Abdel Kareem
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1/2
Y1 - 2021/1/2
N2 - 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 of chemotherapy, reduces side effects such as neutropenia, intestinal mucositis and infections, and extends overall survival. This review highlights the critical contribution of E‐selectin and its specific antagonist, uproleselan, in the regulation of cancer growth, dissemination, and drug resistance in the context of the bone marrow microenvironment.
AB - 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 of chemotherapy, reduces side effects such as neutropenia, intestinal mucositis and infections, and extends overall survival. This review highlights the critical contribution of E‐selectin and its specific antagonist, uproleselan, in the regulation of cancer growth, dissemination, and drug resistance in the context of the bone marrow microenvironment.
KW - Cancer
KW - E‐selectin
KW - Selectins
KW - Uproleselan
UR - http://www.scopus.com/inward/record.url?scp=85100186903&partnerID=8YFLogxK
U2 - 10.3390/cancers13020335
DO - 10.3390/cancers13020335
M3 - Review article
C2 - 33477563
AN - SCOPUS:85100186903
SN - 2072-6694
VL - 13
SP - 1
EP - 15
JO - Cancers
JF - Cancers
IS - 2
M1 - 335
ER -