Soluble c-Met Levels Correlated With Tissue c-Met Protein Expression in Patients With Advanced Non–Small-Cell Lung Cancer

Gao, Hong‐Fei; Li, Anna; Yang, Jing; Chen, Zhihong; Xie, Zhi; Zhang, Xuchao; Su, Jian; Lou, Na-Na; Yan, Hong‐Hong; Han, Jie-Fei; Wu, Yi‐Long

doi:10.1016/j.cllc.2016.06.008

Cited by 13 publications

(9 citation statements)

References 20 publications

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“…The β chain in the extracellular domain can be proteolytically cleaved and released as scMet. Consistent with our findings, Gao et al recently reported a significant correlation between scMet levels and NSCLC tumor cMet protein expression, and that patients with high scMet levels had poor OS [34]. In our study, tumor measures of HGF/cMet pathway activation were not associated with better survival outcomes.…”

Section: Discussionsupporting

confidence: 92%

“…No correlations among baseline circulating markers were found. The soluble cMet protein has been shown to correlate with tumor cMet protein expression in patients with non-small-cell lung cancer (NSCLC) [34]. Here, soluble HGF was correlated with tumor cMet (r = 0.62, p = 0.056), HGF (r = 0.54, p = 0.106) and the cMet-HGF complex (r = 0.65, p = 0.044) and soluble cMet was correlated with the cMet-HGF complex (r = 0.58, p = 0.0677).…”

Section: Prognostic Biomarkersmentioning

confidence: 99%

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Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

Bauman

Ohr

Gooding

et al. 2020

Cancers

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Cetuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance. This Phase I study evaluated the combination of cetuximab and ficlatuzumab, an anti-HGF mAb, in patients with recurrent/metastatic HNSCC. The primary objective was to establish the recommended Phase II dose (RP2D). Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mechanistic tumor-intrinsic and immune biomarkers were explored. Thirteen patients enrolled with no dose-limiting toxicities observed at any dose tier. Three evaluable patients were treated at Tier 1 and nine at Tier 2, which was determined to be the RP2D (cetuximab 500 mg/m2 and ficlatuzumab 20 mg/kg every 2 weeks). Median PFS and OS were 5.4 (90% CI = 1.9–11.4) and 8.9 (90% CI = 2.7–15.2) months, respectively, with a confirmed ORR of 2 of 12 (17%; 90% CI = 6–40%). High circulating soluble cMet levels correlated with poor survival. An increase in peripheral T cells, particularly the CD8+ subset, was associated with treatment response whereas progression was associated with expansion of a distinct myeloid population. This well-tolerated combination demonstrated promising activity in cetuximab-resistant, advanced HNSCC.

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Section: Discussionsupporting

confidence: 92%

Section: Prognostic Biomarkersmentioning

confidence: 99%

Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

Bauman

Ohr

Gooding

et al. 2020

Cancers

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“…The OS was 9.5 vs. 22.2 months for patients with high sMet levels (>766 ng/mL) compared with patients having low levels of sMet (<766 ng/mL, respectively, p < .001). The average plasma sMET concentration was significantly higher in tissue MET-positive patients compared to subjects with MET-negative tumors or healthy individuals [57]. The results of multivariate analysis in another study suggested that the sMet concentration was the strongest prognostic factor for PFS after EGFR-TKI therapy (HR 3.583, 95% CI 1.379-9.312) [181].…”

Section: Iv-circulating Met Levels As Diagnostic and Prognostic Biomamentioning

confidence: 97%

“…Several clinical studies have addressed these issues and reported MET aberrations as indicators of short survival and clinicopathological features of advanced disease in diverse types of cancer, such as gastric [52], colorectal [53], breast [54], hepatocellular [55], pancreatic [56], and lung cancer [57]. In addition, the predictive role of MET dysregulation has been explored in different settings, and some results indicate improved Figure 2.…”

Section: I-a-the Importance Of Hgf/met Aberrations As Clinical Biomarmentioning

confidence: 99%

“…Several studies have investigated the potential utility of the soluble truncated ectodomain of MET protein (sMET) as a biomarker in different types of cancer and the correlation between sMET and tissue MET protein expression ( Table 3). Most of these studies have reported that circulating MET correlates with tumor tissue expression levels [57,175,177,179,180], although this idea was rejected by one report [55]. In a study of 198 patients with NSCLC, Gao et al observed that the plasma sMET levels were significantly correlated with tissue MET protein expression levels (p < .001).…”

Section: Iv-circulating Met Levels As Diagnostic and Prognostic Biomamentioning

confidence: 99%

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HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Moosavi

Giovannetti

Saso³

et al. 2019

Critical Reviews in Clinical Laboratory Sciences

129

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Cancer is a major cause of death worldwide. MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer. The HGF/MET pathway has emerged as an important actionable target across many solid tumors; therefore, biomarker discovery becomes essential in order to guide clinical intervention and patient stratification with the aim of moving towards personalized medicine. The focus of this review is on how the aberrant activation of the HGF/MET pathway in tumor tissue or the circulation can provide diagnostic and prognostic biomarkers and predictive biomarkers of drug response. Many meta-analyses have shown that aberrant activation of the MET pathway in tumor tissue, including MET gene overexpression, gene amplification, exon 14 skipping and other activating mutations, is almost invariably associated with shorter survival and poor prognosis. Most meta-analyses have been performed in non-small cell lung cancer (NSCLC), breast, head and neck cancers as well as colorectal, gastric, pancreatic and other gastrointestinal cancers. Furthermore, several studies have shown the predictive value of MET biomarkers in the identification of patients who gain the most benefit from HGF/MET targeted therapies administered as single or combination therapies. The highest predictive values have been observed for response to foretinib and savolitinib in renal cancer, as well as tivantinib in NSCLC and colorectal cancer. However, some studies, especially those based on MET expression, have failed to show much value in these stratifications. This may be rooted in lack of standardization of methodologies, in particular in scoring systems applied in immunohistochemistry determinations or absence of oncogenic addiction of cancer cells to the MET pathway, despite detection of overexpression. Measurements of amplification and mutation aberrations are less likely to suffer from these pitfalls. Increased levels of MET soluble ectodomain (sMET) in circulation have also been associated with poor prognosis; however, the evidence is not as strong as it is with tissue-based biomarkers. As a diagnostic biomarker, sMET has shown its value in distinguishing cancer patients from healthy individuals in prostate and bladder cancers and in melanoma. On the other hand, increased circulating HGF has also been presented as a valuable prognostic and diagnostic biomarker in many cancers; however, there is controversy on the predictive value of HGF as a biomarker. Other biomarkers such as circulating tumor DNA (ctDNA) and tumor HGF levels have also been briefly covered. In conclusion, HGF/MET aberrations can provide valuable diagnostic, prognostic and predictive biomarkers and represent vital assets for personalized cancer therapy.

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Prognostic utility of the ovarian cancer secretome: a systematic investigation

Kamble

Breed

Pawar

et al. 2022

Arch Gynecol Obstet

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Soluble c-Met Levels Correlated With Tissue c-Met Protein Expression in Patients With Advanced Non–Small-Cell Lung Cancer

Cited by 13 publications

References 20 publications

Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Prognostic utility of the ovarian cancer secretome: a systematic investigation

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