New treatment strategies for advanced-stage gastrointestinal stromal tumours

Klug, Lillian R.; Khosroyani, Homma M; Kent, Jason D; Heinrich, Michael C.

doi:10.1038/s41571-022-00606-4

Cited by 70 publications

(48 citation statements)

References 164 publications

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“…First, on‐target secondary mutations have been studied a lot, which spurs the enthusiasm for finding the next‐generation inhibitors with fewer resistance liabilities, such as ABL TKIs in CML, EGFR and ALK TKIs in lung cancer, and KIT TKIs in GISTs. 75 , 756 , 761 Second, overexpression or amplification of other kinases with similar functions as the drugged kinase can cause the acquisition of “bypass” signaling pathways. 762 , 763 Multikinase inhibitors having the ability to target multiple targets can be applied for targeting “bypass” signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

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Small molecule inhibitors targeting the cancers

Liu

Chen

Zhang

et al. 2022

MedComm

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Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

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Section: Discussionmentioning

confidence: 99%

“…GISTs without KIT and PDGFRA mutations can be divided into SDH‐deficient and SDH‐competent GISTs. 75 , 76 …”

Section: Selective Small Molecule Kinase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors targeting the cancers

Liu

Chen

Zhang

et al. 2022

MedComm

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“…Imatinib, an abl, c-KIT and PDGF-R tyrosine kinase inhibitor (TKI), constitutes the empiric treatment when the mutational status of the disease remains unknown and the first line of treatment in KIT and PDGFRA positive metastatic, inoperable GISTs. The D842V mutation in PDGFRA comprises a therapeutic exception and is being treated with avapritinib while KIT and PDGFRA wild type tumors are treated with sunitinib or regorafinib[ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis in gastrointestinal stromal tumors: From bench to bedside

Papadakos¹,

Tsagkaris²,

Papadakis³

et al. 2022

WJGO

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Gastrointestinal stromal tumors (GISTs) are rare neoplasms with an estimated incidence from 0.78 to 1-1.5 patients per 100000. They most commonly occur in the elderly during the eighth decade of life affecting predominantly the stomach, but also the small intestine, the omentum, mesentery and rectosigmoid. The available treatments for GIST are associated with a significant rate of recurrent disease and adverse events. Thorough understanding of GIST’s pathophysiology and translation of this knowledge into novel regimens or drug repurposing is essential to counter this challenge. The present review summarizes the existing evidence about the role of angiogenesis in GIST’s development and progression and discusses its clinical underpinnings.

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“…Their action mechanism is based on competing with adenosine triphosphate (ATP) for binding to the ATP-binding site of the kinase domain in order to block or reduce the phosphorylation of tyrosine kinase and, ultimately, exert anti-tumor effects ( Cammarota et al, 2022 ; Yang et al, 2022 ; Yao et al, 2022 ). TKIs are widely used in the treatment of small-cell lung cancer (SCLC) ( Hwang et al, 2021 ), non-small cell lung cancer (NSCLC) ( Lin et al, 2022 ; Ten et al, 2022 ), gastrointestinal mesenchymal tumor (GIST) ( Mohammadi and Gelderblom, 2021 ; Foo et al, 2022 ; Klug et al, 2022 ), hepatocellular liver cancer (HCC) ( Decraecker et al, 2021 ), renal cancer (RCC) ( Fogli et al, 2020 ; Pedersen et al, 2021 ), and other cancers owing to their high selectivity and low adverse effects when compared with those of the traditional cytotoxic anticancer drugs ( Xing et al, 2021 ). Sorafenib is the first first-line oral small molecule TKI approved by the U.S. Food and Drug Administration (FDA) for HCC, ushering in a new era of molecular targeting in HCC ( Di et al, 2013 ; Decraecker et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Rapid Determination of 9 Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma in Human Plasma by QuEChERS-UPLC-MS/MS

et al. 2022

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A reliable and rapid method employing QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) pretreatment coupled with ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was successfully developed and validated for the analysis of nine tyrosine kinase inhibitors (TKIs) in human plasma. Biological samples were extracted with acetonitrile and salted out with 350 mg of anhydrous magnesium sulfate (MgSO4), followed by purification with 40 mg of ethyl enediamine-N-propylsilane (PSA) adsorbents. All analytes and internal standards (IS) were separated on the Hypersil GOLD VANQUISH C18 (2.1 mm × 100 mm, 1.9 μM) column using the mobile phases composed of acetonitrile (phase A) and 0.1% formic acid in water (phase B) for 8.0 min. Detection was performed by selection reaction monitoring (SRM) in the positive ion electrospray mode. Lenvatinib, sorafenib, cabozantinib, apatinib, gefitinib, regorafenib, and anlotinib rendered good linearity over the range of 0.1–10 ng/ml, and 1–100 ng/ml for tivantinib and galunisertib. All linear correlation coefficients for all standard curves were ≥ 0.9966. The limits of detection (LOD) and the limits of quantitation (LOQ) ranged from 0.003 to 0.11 ng/ml and 0.01–0.37 ng/ml, respectively. The method was deemed satisfactory with an accuracy of -7.34–6.64%, selectivity, matrix effect (ME) of 90.48–107.77%, recovery, and stability. The proposed method is simple, efficient, reliable, and applicable for the detection of TKIs in human plasma samples as well as for providing a reference for the clinical adjustment of drug administration regimen by monitoring the drug concentrations in the plasma of patients.

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New treatment strategies for advanced-stage gastrointestinal stromal tumours

Cited by 70 publications

References 164 publications

Small molecule inhibitors targeting the cancers

Small molecule inhibitors targeting the cancers

Angiogenesis in gastrointestinal stromal tumors: From bench to bedside

Rapid Determination of 9 Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma in Human Plasma by QuEChERS-UPLC-MS/MS

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