Small-Molecule Protein Kinases Inhibitors and the Risk of Fungal Infections

Katie Bechman, James B. Galloway, Kevin L. Winthrop

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Purpose of Review: This review discusses fungal infections associated with licenced small-molecule protein kinase inhibitors. For each major drug class, the mechanism of action and targeted pathways and the impact on host defence against fungi are described. Recent Findings: Protein kinase inhibitors are successfully used in the treatment of malignancies and immune-mediated diseases, targeting signalling pathways for a broad spectrum of cytokines and growth-stimuli. These agents predispose to fungal infections by the suppression of integral components of the adaptive and innate immune response. Summary: The greatest risk of fungal infections is seen with bruton tyrosine kinase inhibitors, e.g. ibrutinib. Infections are also reported with agents that target mTOR, Janus kinase and break point cluster (Bcr) gene–Abelson (Abl) tyrosine kinase (BCR-ABL). The type of fungal infection fits mechanistically with the specific pathway targeted. Infections are often disseminated and present soon after the initiation of therapy. The pharmacokinetic profile, possibility of off-target kinase inhibition, and underlying disease pathology contribute to infection risk.

Original languageEnglish (US)
Pages (from-to)229-243
Number of pages15
JournalCurrent Fungal Infection Reports
Volume13
Issue number4
DOIs
StatePublished - Dec 1 2019

Fingerprint

Mycoses
Protein Kinase Inhibitors
Infection
Janus Kinases
Immune System Diseases
Adaptive Immunity
Innate Immunity
Protein-Tyrosine Kinases
Fungi
Phosphotransferases
Pharmacokinetics
Pathology
Cytokines
Growth
Pharmaceutical Preparations
Neoplasms
Therapeutics

Keywords

  • BCR-ABL inhibitor
  • BTK inhibitor
  • Fungal infections
  • JAK inhibitor
  • mTOR inhibitor
  • Small-molecule protein kinases inhibitors

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Small-Molecule Protein Kinases Inhibitors and the Risk of Fungal Infections. / Bechman, Katie; Galloway, James B.; Winthrop, Kevin L.

In: Current Fungal Infection Reports, Vol. 13, No. 4, 01.12.2019, p. 229-243.

Research output: Contribution to journalReview article

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