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

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.

journal_name

Pharmacol Ther

authors

Abdel-Azim H,Sun W,Wu L

doi

10.1016/j.pharmthera.2019.107403

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

107403

eissn

0163-7258

issn

1879-016X

pii

S0163-7258(19)30152-4

journal_volume

204

pub_type

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