Strategies to generate functionally normal neutrophils to reduce infection and infection-related mortality in cancer chemotherapy.

Hisham Abdel-Azim, Weili Sun, Lingtao Wu

Journal: Pharmacology & therapeutics 2020;204():107403

PMID: 31470030

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Abstract

Neutrophils form an essential part of innate immunity against infection. Cancer chemotherapy-induced neutropenia (CCIN) is a condition in which the number of neutrophils in a patient's bloodstream is decreased, leading to increased susceptibility to infection. Granulocyte colony-stimulating factor (GCSF) has been the only approved treatment for CCIN over two decades. To date, CCIN-related infection and mortality remain a significant concern, as neutrophils generated in response to administered GCSF are functionally immature and cannot effectively fight infection. This review summarizes the molecular regulatory mechanisms of neutrophil granulocytic differentiation and innate immunity development, dissects the biology of GCSF in myeloid expansion, highlights the shortcomings of GCSF in CCIN treatment, updates the recent advance of a selective retinoid agonist that promotes neutrophil granulocytic differentiation, and evaluates the benefits of developing GCSF biosimilars to increase access to GCSF biologics versus seeking a new mode to fundamentally advance GCSF therapy for treatment of CCIN.

Address: Pediatric Hematology-Oncology, Blood and Marrow Transplantation, Children's Hospital Los Angeles Saban Research Institute, University of Southern California Keck School of Medicine, 4650 Sunset Blvd, Los Angeles, CA 90027, USA.; Pediatric Hematology-Oncology, City of Hope National Medical Center, 1500 E. Duarte road, Duarte, CA 91010, USA.; Research and Development, Therapeutic Approaches, 2712 San Gabriel Boulevard, Rosemead, CA 91770, USA. Electronic address: [email protected].

DOI: 10.1016/j.pharmthera.2019.107403

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MeSH Terms: Antineoplastic Agents, Biosimilar Pharmaceuticals, Cell Differentiation, Granulocyte Colony-Stimulating Factor, Humans, Immunity, Innate, Infections, Neutropenia, Neutrophils