Genetic polymorphisms in angiogenesis-related genes are associated with worse progression-free survival of patients with advanced gastrointestinal stromal tumours treated with imatinib

Verboom, Michiel C.; Kloth, Jacqueline S. L.; Swen, Jesse J.; Straaten, Tahar van der; Bovée, Judith V.M.G.; Sleijfer, Stefan; Reyners, Anna K.L.; Mathijssen, Ron H.J.; Guchelaar, Henk‐Jan; Steeghs, Neeltje; Gelderblom, Hans

doi:10.1016/j.ejca.2017.09.025

Cited by 17 publications

(9 citation statements)

References 29 publications

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“…Similarly, forty-nine single nucleotide polymorphisms (SNPs) involved in the pharmacokinetic and pharmacodynamic pathway of sunitinib were associated with progression-free survival (PFS) and overall survival (OS) in 127 patients with advanced GIST treated with sunitinib (Kloth et al, 2018, p. 201). Similar results were found for genetic polymorphisms related to angiogenesis which modified outcomes of patients with GIST treated with imatinib (Verboom et al, 2017).…”

Section: Role Of Genetic Polymorphismsupporting

confidence: 79%

Major pitfalls of protein kinase inhibitors prescription: A review of their clinical pharmacology for daily use

Gougis

Funck‐Brentano

Paci

et al. 2019

Critical Reviews in Oncology/Hematology

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Protein kinase inhibitors (PKI) are a growing class of anticancer agents. They are prescribed with flat doses, and their oral administration is associated with interindividual variability in exposure. Patients can be over-or underexposed, due to numerous factors. We reviewed key pharmacokinetic concepts and mechanisms by which PKIs prescription could be altered. Challenging situations that could lead to increased toxicity or to therapeutic failure are described and recommendation for clinicians are proposed. Finally, the interest of therapeutic drug monitoring and indications for its use in daily practice is discussed.

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Section: Role Of Genetic Polymorphismsupporting

confidence: 79%

Major pitfalls of protein kinase inhibitors prescription: A review of their clinical pharmacology for daily use

Gougis

Funck‐Brentano

Paci

et al. 2019

Critical Reviews in Oncology/Hematology

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“…In addition, Masago et al have shown that VEGFA -1154 is an independent prognostic factor for NSCLC patients (54). Similarly, Verboom et al have reported that rs1570360 is associated with PFS in patients with advanced GIST receiving imatinib (55).…”

Section: Discussionmentioning

confidence: 97%

Genetic Variations of VEGFA Gene Are Associated With Infiltration of Adjacent Tissues and the Clinical Outcome of Patients With Nasopharyngeal Carcinoma

et al. 2020

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Background/Aim: The aim of the present study was to investigate the clinical significance of 7 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA), endothelin receptor type A (EDNRA), nibrin (NBS1) and Fas cell surface death receptor (FAS) genes in patients with nasopharyngeal carcinoma (NPC). Patients and Methods: Genomic DNA was extracted from the peripheral blood specimens of 60 patients. Genotyping of 4 VEGFA polymorphisms, namely VEGFA-1154 G/A (rs1570360),-2578 A/C (rs699947),-1498 C/T (rs833061) and +936 C/T (rs3025039), as well as EDNRA SNP p.His323 (rs5333), NBS1 p.E185Q (rs1805794) and FAS-671 A/G (rs1800682) was performed by using Sanger sequencing. Results: The VEGFA +936 CC genotype was more frequent in tumors with bilateral infiltration of pterygoid plates compared to those with ipsilateral (76.9% vs. 69.6%, p=0.008) and no infiltration of pterygoid plates (76.9% vs. 68.8%, p=0.023). VEGFA-2578, VEGFA-1154 and VEGFA +936 were significantly associated with infiltration to the pterygoid processes (p=0.011, p=0.041 and p=0.032, respectively). EDNRA H323H TT genotype was marginally associated with infiltration to the ipsilateral medial pterygoid muscles (p=0.045). A trend towards longer overall survival was observed for VEGFA-2578 CC as compared to AC (HR=0.24, p=0.060). Conclusion: The studied VEGFA SNPs seem to be associated with the local extension of the NPC and maybe with the clinical outcome of this patient group. Nasopharyngeal carcinoma (NPC) is a rare human malignancy with an annual incidence of 0.1-1.1/100,000 people with Caucasian origin in western countries.

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“…Several ex vivo studies of GIST specimens have demonstrated that microvessel density is associated with VEGF expression and closely related to the prognosis of the disease (23, 24). Recently, Verboom et al proposed that SNPs in the genes encoding for VEGFR2 was associated with PFS in patients with advanced GISTs treated with imatinib (25). Consolino et al suggested that VEGFR2 and VEGFR3 expression may be related to progression of imatinib-resistant GISTs, and the direct targeting of the receptors may have the potential to decrease tumor growth by the inhibition of angiogenesis (26).…”

Section: Discussionmentioning

confidence: 99%

Apatinib Treatment in Metastatic Gastrointestinal Stromal Tumor

et al. 2019

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Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The clinical management of patients with metastatic GISTs is exceptionally challenging due to their poor prognosis. Apatinib is a multiple tyrosine kinase inhibitor. Here, we present the unique case with metastatic GISTs who derived clinical benefit from apatinib following the failure of imatinib and sunitinib. Case presentation: A 57-year-old man was admitted to our hospital diagnosed with metastatic and recurrent GISTs following surgical resection. Fifty-four months after the first-line imatinib treatment, he developed progressive disease and then was treated with cytoreductive surgery combined with imatinib. Disease progression occurred after 7 months. He then received second-line sunitinib and achieved a progression-free survival of 11 months. Apatinib mesylate was then administered. Follow-up imaging revealed a stable disease. Progression-free survival following apatinib therapy was at least 8 months. The only toxicities were hypertension and proteinuria, which were both controllable and well-tolerated. Conclusions: Treatment with apatinib provides an additional option for the treatment of patients with GISTs refractory to imatinib and sunitinib.

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Genetic polymorphisms in angiogenesis-related genes are associated with worse progression-free survival of patients with advanced gastrointestinal stromal tumours treated with imatinib

Cited by 17 publications

References 29 publications

Major pitfalls of protein kinase inhibitors prescription: A review of their clinical pharmacology for daily use

Major pitfalls of protein kinase inhibitors prescription: A review of their clinical pharmacology for daily use

Genetic Variations of VEGFA Gene Are Associated With Infiltration of Adjacent Tissues and the Clinical Outcome of Patients With Nasopharyngeal Carcinoma

Apatinib Treatment in Metastatic Gastrointestinal Stromal Tumor

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