Kinase inhibitors developed for treatment of hematologic malignancies: implications for immune modulation in COVID-19.
Blood Adv
; 5(3): 913-925, 2021 02 09.
Article
in English
| MEDLINE | ID: covidwho-1072925
ABSTRACT
Tyrosine kinase inhibitors (TKIs) are used to target dysregulated signaling pathways in virtually all hematologic malignancies. Many of the targeted signaling pathways are also essential in nonmalignant immune cells. The current coronavirus severe acute respiratory syndrome coronavirus 2 pandemic catalyzed clinical exploration of TKIs in the treatment of the various stages of COVID-19, which are characterized by distinct immune-related complications. Most of the reported effects of TKIs on immune regulation have been explored in vitro, with different class-specific drugs having nonoverlapping target affinities. Moreover, many of the reported in vivo effects are based on artificial animal models or on observations made in symptomatic patients with a hematologic malignancy who often already suffer from disturbed immune regulation. Based on in vitro and clinical observations, we attempt to decipher the impact of the main TKIs approved or in late-stage development for the treatment of hematological malignancies, including inhibitors of Bruton's tyrosine kinase, spleen tyrosine kinase, BCR-Abl, phosphatidylinositol 3-kinase/ mammalian target of rapamycin, JAK/STAT, and FMS-like tyrosine kinase 3, to provide a rationale for how such inhibitors could modify clinical courses of diseases, such as COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Hematologic Neoplasms
/
Protein Kinase Inhibitors
/
Adaptive Immunity
/
COVID-19
/
Immunity, Innate
Type of study:
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Humans
Language:
English
Journal:
Blood Adv
Year:
2021
Document Type:
Article
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