c-Met targeting in advanced gastric cancer: An open challenge

Marano, Luigi; Chiari, Rita; Fabozzi, Alessio; Vita, Ferdinando De; Boccardi, Virginia; Roviello, Giandomenico; Petrioli, Roberto; Marrelli, Daniele; Roviello, Franco; Patriti, Alberto

doi:10.1016/j.canlet.2015.05.028

Cited by 71 publications

(54 citation statements)

References 107 publications

(127 reference statements)

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“…However, a phase III study of rilotumumab (RILOMET-1) was stopped early due to an increased number of deaths in the rilotumumab and chemotherapy treatment arm when compared to the chemotherapy treatment arm [36]. Unfortunately, preliminary results of a phase II study of onartuzumab in combination with mFOLFOX6 in metastatic HER2-negative gastric cancer revealed a higher rate of serious toxicities in the experimental arm but a similar progression-free survival [37]. Due to these disappointing results, the METGastric phase III study was recently stopped.…”

Section: Discussionmentioning

confidence: 99%

“…In a phase I trial, two of four patients who had MET-amplified gastric or esophageal junction tumors experienced tumor shrinkage upon crizotinib treatment [19]. Meanwhile, in a phase I study of AMG 337, five of seven gastric cancer patients harboring MET amplification achieved an objective response [37]. Building on these promising results, a phase II study of AMG337 in gastric cancer is ongoing.…”

Section: Discussionmentioning

confidence: 99%

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MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer

Yang

Shen

et al. 2015

Gastric Cancer

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Background Currently, only trastuzumab, ramucirumab, and apatinib effectively treat gastric cancer. Thus, additional novel targets are required for this disease. Methods We investigated the immunohistochemical and fluorescence in situ hybridization expression of MET, ROS1, and ALK in four gastric cell lines and a cohort of 98 gastric cancer patients. Crizotinib response was studied in vitro and in vivo. Results Crizotinib potently inhibited in vitro cell growth in only one cell line, which also showed MET amplification. A positive correlation between crizotinib sensitivity and MET overexpression was observed (P = 0.045) in the histoculture drug response assay. Meanwhile, patientderived tumor xenograft mouse models transplanted with tissues with higher MET protein expression displayed a highly selective sensitivity to crizotinib. In the 98 patients, MET overexpression was found in 42 (42.9 %) and MET was amplified in 4 (4.1 %). ROS1 and ALK overexpression were found in 25 (25.5 %) and 0 patients, respectively. However, none of the patients screened harbored ALK or ROS1 rearrangements. No significant association was found between overall survival and MET or ROS1 status. We also observed a stage IV gastric cancer patient with MET amplification who experienced tumor shrinkage and clinical benefit after 3 weeks of crizotinib as fourth-line treatment. Conclusions Crizotinib may induce clinically relevant anticancer effects in MET-overexpressed or MET-amplified gastric cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer

Yang

Shen

et al. 2015

Gastric Cancer

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“…The efficiency of ABT-700 as a c-Met inhibitor has been evaluated in both monotherapy and in association with folinic acid, docetaxel or 5-fluorouracil, cetuximab, and irinotecan or erlotinib. 111 …”

Section: Anti-met Monoclonal Antibodiesmentioning

confidence: 99%

“…8 AMG-337 is a highly selective, oral, ATP-competitive c-Met inhibitor that directly blocks the c-Met pathway and interrupts c-Met signal transduction pathways which in tumors with overexpressing c-Met can induce cell death. 111,126 More studies in cancer cell lines get from NSCLC, gastric, and esophageal cancer approved that the in vitro anti-proliferative activity of AMG 337 is connected with augmentation of c-Met. Furthermore, therapy with AMG 337 in those cell lines prevented downstream MAPK and PI3K signaling pathways, which resulted in growth suppression as proved by an agglomeration of cells that stay in the G1 phase of the cell cycle and diminution of DNA synthesis and accelerate cell apoptosis.…”

Section: Tk Inhibitorsmentioning

confidence: 99%

The c-Met receptor: Implication for targeted therapies in colorectal cancer

et al. 2017

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c-Met (mesenchymal-epithelial transition factor) is a tyrosine kinase receptor activated by hepatocyte growth factor and regulates multiple biological processes, such as cell scattering, survival, and proliferation. Aberrant c-Met signaling has been implicated in a variety of cancer types, including colorectal cancer. c-Met is genetically altered through various mechanisms that is associated with colorectal cancer progression and metastasis. Especially, in colorectal cancer, preclinical evidence for the aberrant activation of the c-Met signaling exists. Accordingly, molecular targeting of c-Met receptor could be a promising strategy, in the treatment of colorectal cancer patients. Recently, it was also shown that crosstalk between c-Met and other cell surface receptors attributes to tumorigenesis and development of therapeutic resistance. Characterization of the molecular mechanisms through which c-Met crosstalks with other receptors in favor of tumor formation and progression remains to explore. This review will describe the mechanisms of aberrant c-Met signaling in colorectal cancer and discuss on additional roles for c-Met receptor through crosstalk with other tyrosine kinase receptors and cell surface proteins in colorectal cancer. Novel therapeutic approaches for c-Met pathway targeting will also be discussed.

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“…However, HER2-overexpressing tumors represent approximately 20 % of the total number of GC [7][8][9]. Unfortunately, with the exception of trastuzumab in HER2-positive GC, recent studies of other agents targeting oncogenic mediators, such as epidermal growth factor receptor (EGFR), mTOR, and c-Met, have not been shown to improve survival [10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis inhibitors in gastric and gastroesophageal junction cancer

et al. 2015

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Despite significant improvements in systemic chemotherapy during the past two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. Unfortunately, although a number of molecular targets have been studied, very few of these agents can be used in a clinical setting. In this review, we summarize the available data on anti-angiogenic agents in advanced/metastatic gastric cancer.

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c-Met targeting in advanced gastric cancer: An open challenge

Cited by 71 publications

References 107 publications

MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer

MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer

The c-Met receptor: Implication for targeted therapies in colorectal cancer

Angiogenesis inhibitors in gastric and gastroesophageal junction cancer

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