Tyrosine kinase inhibitors and immune checkpoint inhibitors-induced thyroid disorders

Jannin, Arnaud; Penel, Nicolas; Ladsous, M.; Vantyghem, M. C.; Cao, Christine Do

doi:10.1016/j.critrevonc.2019.05.015

Cited by 55 publications

(52 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…inhibition. 29 The thyroid, in fact, is a highly vascularized organ and its blood flow is mainly dependent on VEGFR. Hence, VEGFR blockade can cause reduced blood flow and parenchymal devascularization, with the typical picture of destructive thyroiditis in the absence of specific autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

“…It is already known that the use of TKI is associated with an increased risk of developing hypothyroidism. The definitive mechanism has not yet been fully defined, but the most probable hypothesis is vascular endothelial growth factor receptor (VEGFR) inhibition . The thyroid, in fact, is a highly vascularized organ and its blood flow is mainly dependent on VEGFR.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thyroid disorders in programmed death 1 inhibitor‐treated patients: Is previous therapy with tyrosine kinase inhibitors a predisposing factor?

Sbardella

Tenuta

Sirgiovanni

et al. 2020

Clinical Endocrinology

View full text Add to dashboard Cite

Background Programmed death 1 (PD‐1) inhibitors are frequently associated with thyroid‐related adverse events (TAEs), but many aspects remain unclear. This study aims to evaluate the incidence and characteristics of such events and to find any predictive factor for its development. Methods We retrospectively analysed data from patients with advanced solid tumours (non‐small‐cell lung carcinoma, renal cell carcinoma, metastatic melanoma) treated with PD‐1 inhibitors (nivolumab, pembrolizumab) in Oncology Unit B, Policlinico Umberto I of Rome, from June 2015 to December 2018. All patients underwent baseline thyroid function evaluations repeated monthly. Results The cohort consisted of 126 patients (66.7% male, mean age 66.4 ± 9.7 years). One hundred and seven received nivolumab and 19 pembrolizumab. Twenty‐three per cent of patients experienced TAEs (mainly CTCAE grade 1), with hypothyroidism in 15.1% (subclinical: 11.9%, overt: 3.2%) and hyperthyroidism in 8.0% (subclinical: 4.8%, overt: 3.2%). Median time to TAE onset was 8.7 ± 6.8 weeks (10.4 ± 7.6 weeks for hypothyroidism, 5.4 ± 3.0 weeks for hyperthyroidism). Most TAEs (89.7%) appeared within the first 3 months, none after 8 months. Most hypothyroid patients (63.2%) had previously been treated with a tyrosine kinase inhibitor (TKI). Logistic regression analysis showed that pretreatment with a TKI was a major predisposing factor for the development of hypothyroidism (OR 9.2, 95% CI: 1.4‐59.9, P = .020). Conclusions TAEs are common during anti‐PD‐1 therapy and usually occur within the first 3 months of treatment. This is the first study evaluating the impact of previous oncologic therapies on TAEs, identifying TKI as a major risk factor for the development of hypothyroidism in patients treated with anti‐PD‐1.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thyroid disorders in programmed death 1 inhibitor‐treated patients: Is previous therapy with tyrosine kinase inhibitors a predisposing factor?

Sbardella

Tenuta

Sirgiovanni

et al. 2020

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

“…Functional enrichment analysis showed that the upregulated genes were enriched in cell division and cell proliferation, which are critical for tumor growth, and that the downregulated genes mainly participated in various metabolic processes, including retinol metabolism, tyrosine metabolism, and drug metabolism/cytochrome P450 pathways, as well as the Wnt signaling pathway, which contributes to carcinogenesis 40–42. A large number of studies have proposed that disorders in metabolism, including retinol metabolism43,44 and tyrosine metabolism,45,46 play important roles in carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

<p>Integrated Analysis To Identify Molecular Biomarkers Of High-Grade Serous Ovarian Cancer</p>

Si¹,

Zhang²,

Cao³

et al. 2019

OTT

View full text Add to dashboard Cite

PurposeOvarian cancer is the leading cause of gynecologic cancer-related death worldwide. Early diagnosis of ovarian cancer can significantly improve patient prognosis. Hence, there is an urgent need to identify key diagnostic and prognostic biomarkers specific for ovarian cancer. Because high-grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer and accounts for the majority of deaths, we identified potential biomarkers for the early diagnosis and prognosis of HGSOC.MethodsSix datasets (GSE14001, GSE18520, GSE26712, GSE27651, GSE40595, and GSE54388) were downloaded from the Gene Expression Omnibus database for analysis. Differentially expressed genes (DEGs) between HGSOC and normal ovarian surface epithelium samples were screened via integrated analysis. Hub genes were identified by analyzing protein–protein interaction (PPI) network data. The online Kaplan-Meier plotter was utilized to evaluate the prognostic roles of these hub genes. The expression of these hub genes was confirmed with Oncomine datasets and validated by quantitative real-time PCR and Western blotting.ResultsA total of 103 DEGs in patients with HGSOC—28 upregulated genes and 75 downregulated genes—were successfully screened. Enrichment analyses revealed that the upregulated genes were enriched in cell division and cell proliferation and that the downregulated genes mainly participated in the Wnt signaling pathway and various metabolic processes. Ten hub genes were associated with HGSOC pathogenesis. Seven overexpressed hub genes were partitioned into module 1 of the PPI network, which was enriched in the cell cycle and DNA replication pathways. Survival analysis revealed that MELK, CEP55 and KDR expression levels were significantly correlated with the overall survival of HGSOC patients (P < 0.05). The RNA and protein expression levels of these hub genes were validated experimentally.ConclusionBased on an integrated analysis, we propose the further investigation of MELK, CEP55 and KDR as promising diagnostic and prognostic biomarkers of HGSOC.

show abstract

“…Eine Reihe von Medikamenten kann eine Autoimmunthyreoiditis mit Funktionsstörungen auslösen. Hierzu zählen Interferon Alpha, Interleukin 2, Tyrosinkinase-Inhibitoren und neuerdings Immun-Checkpoint-Inhibitoren [18,19]. Ein Absetzen der auslösenden Substanz ist in der Regel aus medizinisch-ethischen Gründen nicht möglich, sodass die Folgen der Autoimmunthyreoiditis einer medikamentösen Behandlung bedürfen.…”

Section: Medikamenteninduzierte Thyreoiditisunclassified

“…Eine iatrogen-induzierte Hypothyreose kann nach Radiojodtherapie und nach Schilddrüsenoperation ohne eine adäquate Substitutionsbehandlung auftreten. Seltene meist vorübergehende Ursachen sind die subakute Thyreoiditis de Quervain, die Postpartum-Thyreoiditis und medikamentös induzierte Funktionsstörungen (Amiodaron, Lithium, Tyrosinkinase-Inhibitoren, Checkpoint-Inhibitoren) [19]. Genetische Funktionsstörungen und Organdys-und -agenesien werden im Kindesalter bereits identifiziert.…”

Section: Hypothyreose Ursachenunclassified

Schilddrüsenfunktionsstörungen

Feldkamp

2019

Klinikarzt

View full text Add to dashboard Cite

ZUSAMMENFASSUNGBei den Schilddrüsenfunktionsstörungen sind Hyperthyreosen in der Klinik bedeutsamer als Hypothyreosen. Ursachen der Hyperthyreose sind bei jüngeren Menschen der Morbus Basedow und bei älteren Menschen eher autonome Funktionsstörungen; seltener sind Kontrastmittel- und Medikamenten-induzierte Hyperthyreosen. Hyperthyreosen werden initial mit Thyreostatika behandelt. Symptomatisch können ergänzend Betablocker gegeben werden. Die hyperthyreote Initialphase einer Hashimoto-Thyreoiditis oder die Hyperthyreose bei subakuter Thyreoiditis wird lediglich symptomatisch therapiert. Je nach Ursache kann mittelfristig eine Radiojodtherapie oder eine Schilddrüsenresektion notwendig werden. Das hypothyreote Koma ist sehr selten und bedarf intensivmedizinischer Behandlung. Leichte TSH-Erhöhungen können zunächst im Verlauf kontrolliert werden und müssen nicht immer behandelt werden. Auf der Intensivstation wird nicht selten ein low T3-/low T4-Syndrom (non-thyroidal illness-syndrome) beobachtet. Dieses benötigt meist keine Therapie.

show abstract

Tyrosine kinase inhibitors and immune checkpoint inhibitors-induced thyroid disorders

Cited by 55 publications

References 131 publications

Thyroid disorders in programmed death 1 inhibitor‐treated patients: Is previous therapy with tyrosine kinase inhibitors a predisposing factor?

Thyroid disorders in programmed death 1 inhibitor‐treated patients: Is previous therapy with tyrosine kinase inhibitors a predisposing factor?

<p>Integrated Analysis To Identify Molecular Biomarkers Of High-Grade Serous Ovarian Cancer</p>

Schilddrüsenfunktionsstörungen

Contact Info

Product

Resources

About