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Review
. 2022 May 11;12(2):e12075.
doi: 10.1002/pul2.12075. eCollection 2022 Apr.

Differentiating pulmonary hypertension associated with protein kinase inhibitors

Joshua A Jacobs  1 , Eiman Jahangir  2 , John J Ryan  3
Affiliations
Review

Differentiating pulmonary hypertension associated with protein kinase inhibitors

Joshua A Jacobs et al. Pulm Circ. .

Abstract

Protein kinase inhibitors (PKIs) have been implicated in pulmonary vascular toxicities including risk factors for at least three of the five World Health Organization groups of pulmonary hypertension (PH). These toxicities include direct drug-induced pulmonary arterial hypertension, an increase in cardiomyopathies, and an increase in interstitial lung disease. On- and off-target toxicities are common within multitargeted PKIs leading to cardiopulmonary toxicities. This review highlights the incidence, possible mechanisms, and management strategies for each group of possible PKI-induced PH. Future identification and clarification of protein kinase pathways for both mechanisms of toxicity and pathophysiology for PH could lead to improvements in patient care in oncology and pulmonary vascular diseases.

Keywords: cancer; dasatinib; protein kinase; pulmonary arterial hypertension; tyrosine kinase.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Mechanism of dasatinib‐induced PAH. PAH, pulmonary arterial hypertension; ROS, reactive oxygen species; sE‐selectin, soluble E‐selectin; sICAM‐1, soluble intercellular adhesion molecule; sVCAM‐1, soluble vascular cell adhesion molecule
Figure 2
Figure 2
Definitions and management of overt cancer therapy‐related left ventricular systolic dysfunction (adapted from ref. [142]). ACEi, angiotensin‐converting enzyme inhibitor; BB, beta‐blocker; BNP, brain natriuretic peptic; LVEF, left ventricular systolic function; NYHA, New York Heart Association; NT‐proBNP, N‐terminal pro b‐type natriuretic peptide; TTE, transthoracic echocardiogram
Figure 3
Figure 3
Connecting PKI groups with the likely WHO PH class. ALK, anaplastic lymphoma kinase; BCR‐ABL1, breakpoint cluster region‐Abelson leukemia gene; BRAF, b‐Raf oncogene; BTK, Bruton's tyrosine kinase; CDK, cyclin‐dependent kinase; ErbB1/EGFR, epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; FLT3, Fms‐like tyrosine kinase 3; JAK, Janus kinase; MEK, mitogen‐activated protein kinase; MET/HGHR, hepatocyte growth factor receptor; mTOR, mechanistic target of rapamycin; PDGFR, platelet‐derived growth factor receptor; PI3K‐δ, phosphoinositide‐3 kinase delta; RET, rearranged during transfection; TRK, tropomyosin receptor kinase; VEGFR, vascular endothelial growth factor receptor
See this image and copyright information in PMC

References

    1. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, Williams PG, Souza R. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. - PMC - PubMed
    1. Galiè N, McLaughlin VV, Rubin LJ, Simonneau G. An overview of the 6th World Symposium on Pulmonary Hypertension. Eur Respir J. 2019;53(1):1802148. - PMC - PubMed
    1. Henson KE, Reulen RC, Winter DL, Bright CJ, Fidler MM, Frobisher C, Guha J, Wong KF, Kelly J, Edgar AB, McCabe MG, Whelan J, Cutter DJ, Darby SC, Hawkins MM. Cardiac mortality among 200000 five‐year survivors of cancer diagnosed at 15 to 39 years of age: the teenage and young adult cancer survivor study. Circulation. 2016;134(20):1519–31. - PMC - PubMed
    1. Moslehi JJ, Deininger M. Tyrosine kinase inhibitor‐associated cardiovascular toxicity in chronic myeloid leukemia. J Clin Oncol. 2015;33(35):4210–8. - PMC - PubMed
    1. National Center for Biotechnology Information . 2021. Available from: https://pubchem.ncbi.nlm.nih.gov/compound