Correlation of plasma crizotinib trough concentration with adverse events in patients with anaplastic lymphoma kinase positive non-small-cell lung cancer

Kurata, Yasuko; Miyauchi, Narumi; Suno, Manabu; Ito, Takahiro; Sendo, Toshiaki; Kiura, Katsuyuki

doi:10.1186/s40780-014-0008-x

Cited by 17 publications

(13 citation statements)

References 17 publications

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“…The steady state crizotinib trough concentration reached in this patient, 304 ng/mL, was in line with crizotinib concentrations described in literature, ranging from respectively 244 to 848 ng/mL in Asian populations [3] and 242 to 319 ng/mL in Caucasian populations [4].…”

Section: Discussionsupporting

confidence: 87%

Administration of crizotinib via jejunostomy tube: A case report

Knapen¹,

Dingemans²,

Croes³

2018

OAJ Clin Case Rep

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Crizotinib is an orally available tyrosine kinase inhibitor, approved for treatment of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangement-positive non-small cell lung cancer (NSCLC). According to the product leaflet, crizotinib capsules should be swallowed whole, and should not be crushed, dissolved or opened. However, this manner of administration is not always possible. At present, literature is lacking regarding the absorption of crizotinib via percutaneous endoscopic jejunostomy (PEJ) tube. We report a case of a patient with ALK+ NSCLC who was administered crizotinib via PEJ tube. An adequate steady state crizotinib trough concentration was reached, resulting in a metabolic response. Safety for the caregiver was ensured since the administration of crizotinib was made without crushing or opening the capsule. This case supports the option for providing crizotinib via PEJ tube in patients who have ALK+ NSCLC and are unable to swallow whole capsules. This option might also apply to the administration of other ALK inhibitors. Keywords Crizotinib, ALK inhibitor, percutaneous endoscopic jejunostomy tube, pharmacokinetics, non-small cell lung cancer.

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Section: Discussionsupporting

confidence: 87%

Administration of crizotinib via jejunostomy tube: A case report

Knapen¹,

Dingemans²,

Croes³

2018

OAJ Clin Case Rep

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“…To determine if MET status influences tumor response to HER2 inhibition, we examined the colony formation and tumor growth of isogenic H2170 clones treated with the HER2 TKIs (lapatinib, ASLAN001) and monoclonal antibodies (trastuzumab and pertuzumab). In contrast to crizotinib that achieved only modest effects at therapeutic doses 29 , lapatinib and trastuzumab both potently inhibited anchorage-independent growth of MET N375S-tGFP cells ( Fig. 6h; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 98%

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma

et al. 2020

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MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables MET N375S to interact with HER2 in a ligandindependent fashion. The resultant MET N375S /HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing MET N375S . These results establish MET N375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies.

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“…Our intracellular target engagement analysis included a diversity set comprising 178 full-length kinases spanning each kinase subfamily, including the well-characterized crizotinib targets MET and ALK. Since engagement is dose dependent, we selected a clinically relevant (C max ) dose of 1 μM crizotinib for the cellular profiling ( Kurata et al., 2015 ). For each kinase tested, a concentration of energy transfer probe was introduced to the culture medium at an optimized concentration as described in Table S1 .…”

Section: Resultsmentioning

confidence: 99%

Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement

Vasta

Corona

Wilkinson

et al. 2018

Cell Chemical Biology

229

274

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SummaryFor kinase inhibitors, intracellular target selectivity is fundamental to pharmacological mechanism. Although a number of acellular techniques have been developed to measure kinase binding or enzymatic inhibition, such approaches can fail to accurately predict engagement in cells. Here we report the application of an energy transfer technique that enabled the first broad-spectrum, equilibrium-based approach to quantitatively profile target occupancy and compound affinity in live cells. Using this method, we performed a selectivity profiling for clinically relevant kinase inhibitors against 178 full-length kinases, and a mechanistic interrogation of the potency offsets observed between cellular and biochemical analysis. For the multikinase inhibitor crizotinib, our approach accurately predicted cellular potency and revealed improved target selectivity compared with biochemical measurements. Due to cellular ATP, a number of putative crizotinib targets are unexpectedly disengaged in live cells at a clinically relevant drug dose.

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Correlation of plasma crizotinib trough concentration with adverse events in patients with anaplastic lymphoma kinase positive non-small-cell lung cancer

Cited by 17 publications

References 17 publications

Administration of crizotinib via jejunostomy tube: A case report

Administration of crizotinib via jejunostomy tube: A case report

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma

Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement

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