Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion‐positive non–small cell lung cancer

Zhang, Limin; Jiang, Tao; Li, Xuefei; Wang, Yan; Zhao, Chao; Zhao, Sha; Liu, Xi; Zhang, Shijia N; Liu, Xiaozhen; Jia, Yijun; Yang, Hui; Shi, Jinpeng; Su, Chunxia; Ren, Shengxiang; Zhou, Caicun

doi:10.1002/cncr.30677

Cited by 39 publications

(30 citation statements)

References 50 publications

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“…High Bim expression is a potential prognostic marker as well as a chemotherapeutic target for cervical cancer (56). The Bim deletion polymorphism was found to be associated with primary resistance to crizotinib in patients with ALK fusion-positive non-small cell lung cancer (57). As such, targeting and manipulating Bim expression or activity may affect the outcomes of human cancers.…”

Section: Discussionmentioning

confidence: 99%

Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells

et al. 2018

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Osteosarcoma (OS) is the most common primary malignant bone tumor worldwide, primarily affecting children and adolescents. The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase that is activated by its co‑activator Cdc20 during the metaphase‑anaphase transition. Apcin is a novel cell‑permeable molecule that blocks the interaction between APC/C and Cdc20. Cdc20 overexpression has been reported in various malignancies and plays an oncogenic role in tumorigenesis and tumor progression. In the present study, the antitumor properties of apcin, an inhibitor of Cdc20, was investigated in OS cell lines. In addition, the possible molecular target by which apcin mediates cell death was explored. Apcin was demonstrated to inhibit OS cell growth and induce significant apoptosis. The invasion and mobile abilities of OS cells were also markedly suppressed by apcin treatment. Furthermore, Bim and p21 were upregulated in OS cells following apcin treatment. The results of the present study indicated that apcin may have therapeutic potential as a treatment for OS and that Cdc20 may be a promising molecular target for chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells

et al. 2018

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“…However, to our knowledge, the mechanisms of primary resistance to ALK inhibitor for these patients remain elusive. And only some primary resistance mechanisms have been hypothesized, such as mutations of the EGFR pathway and BIM polymorphisms (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

TP53 mutations predict for poor survival in ALK rearrangement lung adenocarcinoma patients treated with crizotinib

Wang¹,

Xu²,

Chen³

et al. 2018

J. Thorac. Dis.

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“…To date, a limited number of biomarkers have been proven to be associated with survival in patients with ALK fusion NSCLC (8,9). c-Kit is a transmembrane tyrosine kinase, with SCF as a ligand, serving an important role in inducing a number of signal transduction pathways, including those of mitogen-activated protein kinase and phosphatidyl inositol 3-kinase/protein kinase B (10,11).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is unknown which patients would benefit more from the second-generation TKIs. To date, only BIM deletion polymorphism and EML4-ALK variants 3a/b have been found to be associated with poor clinical response of patients with ALK fusion NSCLC to crizotinib (8,9). Therefore, further studies of the intrinsic mechanism of resistance to crizotinib would be beneficial for improved decision-making in TKI selection for first-line treatment.…”

Section: Discussionmentioning

confidence: 99%

Predictive and prognostic value of phosphorylated c‑KIT and PDGFRA in advanced non‑small cell lung cancer harboring ALK fusion

et al. 2019

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Secondary KIT gene amplification leads to tyrosine kinase inhibitor resistance in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC). The presence of the 4q12 amplicon causes the activation of downstream mast/stem cell growth factor receptor Kit (c-Kit) or platelet-derived growth factor receptor α (PDGFRA) signaling pathways. Therefore, in the present study, the association between the functional proteins phosphorylated c-Kit (p-c-Kit) and phosphorylated PDGFRA (p-PDGFRA) and the prognosis of ALK fusion NSCLC was investigated. Advanced stage NSCLC samples with ALK fusion were tested for their p-c-Kit and p-PDGFRA content by immunohistochemical staining, and for its association with crizotinib efficacy and the survival of the patients. Of 64 eligible ALK-positive patients with NSCLC, 30 (46.9%) were p-c-Kit-positive and 10 (15.7%) were p-PDGFRA-positive. Brain metastases were more common in ALK-positive cases that were p-PDGFRA-positive compared with those who were p-PDGFRA-negative. ALK-positive patients treated with crizotinib, who exhibited high levels of p-c-Kit had significantly lower progression-free survival times than those with low levels. In addition, the patients with high levels of p-c-Kit exhibited lower overall survival times than those with low levels. Furthermore, multivariate analysis indicated that high levels of p-c-Kit in patients with ALK fusion was the only significant predictive factor for crizotinib efficacy and was a prognostic factor for poor overall survival time. However, no statistically significant difference was observed in the survival of patients with different p-PDGFRA levels. p-PDGFRA was more frequently expressed in the ALK-positive cases with brain metastasis. c-Kit signaling activation may be associated with poor efficacy of crizotinib and poor prognosis in advanced ALK fusion NSCLC.

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Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion‐positive non–small cell lung cancer

Abstract: The Bim deletion polymorphism was found to be associated with poor clinical response to crizotinib in patients with ALK fusion-positive NSCLC. Cancer 2017;123:2927-35. © 2017 American Cancer Society.

Cited by 39 publications

References 50 publications

Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells

Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells

TP53 mutations predict for poor survival in ALK rearrangement lung adenocarcinoma patients treated with crizotinib

Predictive and prognostic value of phosphorylated c‑KIT and PDGFRA in advanced non‑small cell lung cancer harboring ALK fusion

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