High Matrix Metalloproteinase 28 Expression is Associated with Poor Prognosis in Pancreatic Adenocarcinoma

Emerging evidence shows that exocytosis plays a key role in tumor development and metastasis. Secernin-1 (SCRN1) is a novel regulator of exocytosis. Our previous work identified SCRN1 as a tumor-associated gene by bioinformatics analysis of transcriptomes. In this study, we demonstrated the aberrant overexpression of SCRN1 at mRNA and protein level in colon cancer. We also revealed that overexpression of SCRN1 was significantly associated with the tumor development and poor prognosis. Experimentsin vitrovalidated that SCRN1 may promote cancer cell proliferation and secretion of matrix metalloproteinase-2/9 (MMP-2/9) proteins to accelerate tumor progression.

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Overexpression of matrix metalloproteinase-7 (MMP-7) correlates with tumor proliferation, and a poor prognosis in non-small cell lung cancer

Lung Cancer ◽

10.1016/j.lungcan.2007.07.005 ◽

2007 ◽

Vol 58 (3) ◽

pp. 384-391 ◽

Cited By ~ 77

Author(s):

Dage Liu ◽

Jun Nakano ◽

Sinya Ishikawa ◽

Hiroyasu Yokomise ◽

Masaki Ueno ◽

...

Keyword(s):

Lung Cancer ◽

Matrix Metalloproteinase ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

Tumor Proliferation ◽

Small Cell Lung ◽

Matrix Metalloproteinase 7

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Updated results of a phase 1 study combining the matrix metalloproteinase 9 inhibitor GS-5745 with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.363 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 363-363 ◽

Cited By ~ 1

Author(s):

Johanna C. Bendell ◽

Manish R. Patel ◽

Carrie Baker Brachmann ◽

Xi Huang ◽

Julia D. Maltzman ◽

...

Keyword(s):

Pancreatic Cancer ◽

Matrix Metalloproteinase ◽

Pancreatic Adenocarcinoma ◽

Phase 1 ◽

Objective Response ◽

Locally Advanced ◽

Matrix Metalloproteinase 9 ◽

Phase 1 Study ◽

Metastatic Setting ◽

Metalloproteinase 9

363 Background: GS-5745 is a monoclonal antibody inhibitor of matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. We present data from patients (pts) with advanced pancreatic adenocarcinoma enrolled in an ongoing multi-indication phase 1 study (NCT01803282) evaluating GS-5745. Methods: Following a monotherapy dose finding stage, pts with locally advanced or metastatic pancreatic cancer received gemcitabine (G) + nab-paclitaxel (Abraxane, A) and GS-5745 800 mg IV every 2 weeks. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Response was assessed every 8 weeks per RECIST version 1.1 criteria. Results: As of April 2016, 36 pts were enrolled (1 continues to receive GS-5745). The most frequently observed adverse events (AEs) of any grade include fatigue (75%), alopecia (55.6%), peripheral edema (55.6%) and nausea (50%). Grade ≥ 3 AEs observed in ≥ 10% of pts included neutropenia (25%), anemia (19.4%) and fatigue (13.9%). The median progression free survival (PFS) for all pts is 7.8 (90% confidence interval (CI) = [6.1, 11]) months (mos), median duration of response (DOR) is 5.8 mos and the objective response rate (ORR) is 44.4%. Of the 31 pts who were treatment naïve in the metastatic setting, median PFS is 9.2 (90% CI = [6.1, 11]) mos, median DOR 5.8 mos and the ORR 51.6%. Median baseline circulating MMP9 was 44.3 (range 12.4-549.6) ng/mL and 31 of 32 patients with post-baseline samples had undetectable MMP9 levels within 8 weeks. Conclusions: GS-5745+GA demonstrated numerically higher ORR and PFS compared to historical data without additional toxicity. Additionally, reductions in circulating MMP9 levels post treatment suggest target engagement by GS-5745 . These results suggest this combination may warrant additional study in first line metastatic pancreatic adenocarcinoma. Clinical trial information: NCT01803282.

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