Personalized therapeutic strategies in HER2-driven gastric cancer

51 Background: Gastric cancer (GC) is a highly heterogeneous disease. Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced GC patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. The aim of this study is to investigate fusion landscape in advanced GC. Methods: A multicenter study in China was initiated from Aug. 2016, and GC patients have been enrolled as of Aug. 2018. To determine the fusion frequency in GC, we analyzed data from 371clinical GC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, 61 patients (16.44%) were identified with fusions, including TMEM45B-FGF3 (3), AXIN1-SMPD3 (3), B3GNTL1-ERBB2 (2), ERBB2-LAMA3 (2), ERBB2-ACLY (2), TRIM24-BRAF (2), ARHGEF1-CD79A (2), FGFR4-UIMC1 (2), MSH2-TTC7A (2), SMARCA4-LDLR (2), GON4L-RIT1 (2), AKT1-CPSF2 (2), GATA6-COLEC12 (2), RICTOR-EFNA5 (2), KAT6A-PLAT (2), ROCK1-CCDC178 (2), HBS1L-MYB (2), SLC30A2-ARID1A (2), MSI2-BIRC5 (2), NOTCH3-UCA1 (2), PIK3C2B-KISS1 (2), RICTOR-OSMR (2), FGFR2-MIR5694 (2), FGFR2-FGFR1 (2), MAN2A2-BLM (2), EGFR-MED15 (1), EML4-ALK(1), GOPC-ROS1 (1), FXR2-TP53 (1), NF1-PSMD11 (1), IRS2-PRKCI (1), FGFR2-KIAA1217(1), FGFR2-TACC2 (1), FGFR3-TACC3 (1). ERBB2, BRAF, EGFR, ALK and ROS1 fusionswere seen in 18.03% (11/61) of advanced Chinese gastric cancer fusion landscape patients. Conclusions: Advanced Chinese gastric cancer fusion landscape is rich, ERBB2, BRAF, EGFR, ALK and ROS1 fusions are rare but potentially druggable in TKIs. Detection of ERBB2, BRAF, EGFR, ALK and ROS1 fusions should be part of comprehensive profiling panels to determine TKIs and direct appropriate combination therapeutic strategies.

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Diagnostic and therapeutic strategies for gastric cancer in the era of precision medicine

Annals of Research Hospitals ◽

10.21037/arh.2017.04.08 ◽

2017 ◽

Vol 1 ◽

pp. 1-1

Author(s):

Kecheng Zhang ◽

Xiaohui Huang ◽

Bo Wei ◽

Xiaosong Wu ◽

Hongqing Xi ◽

...

Keyword(s):

Gastric Cancer ◽

Precision Medicine ◽

Therapeutic Strategies

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MicroRNA expression and its implication for the diagnosis and therapeutic strategies of gastric cancer

Cancer Letters ◽

10.1016/j.canlet.2010.07.018 ◽

2010 ◽

Vol 297 (2) ◽

pp. 137-143 ◽

Cited By ~ 49

Author(s):

Jianbo Wang ◽

Qingwei Wang ◽

Hong Liu ◽

Bo Hu ◽

Wei Zhou ◽

...

Keyword(s):

Gastric Cancer ◽

Therapeutic Strategies ◽

Microrna Expression

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Palliative Gastrectomy versus Gastrojejunostomy for advanced Gastric cancer with outlet obstruction: a propensity score matching analysis

BMC Cancer ◽

10.1186/s12885-021-07904-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiao-Jiang Chen ◽

Guo-Ming Chen ◽

Yi-Cheng Wei ◽

Hong Yu ◽

Xi-Cheng Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Propensity Score ◽

Advanced Gastric Cancer ◽

Propensity Score Matching ◽

Protective Factor ◽

Late Complication ◽

Outlet Obstruction ◽

Therapeutic Strategies ◽

Complication Rates ◽

Palliative Gastrectomy

Abstract Background Gastric outlet obstruction (GOO) is a late complication of advanced gastric cancer, and it is controversial how to select the therapeutic strategies: gastrojejunostomy and palliative gastrectomy? Therefore, this study was to compare the surgical and survival outcomes of gastrojejunostomy and palliative gastrectomy. Methods In total, 199 gastric cancer patients with outlet obstruction treated by surgery between January 2000 and December 2015 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Patients were divided into gastrojejunostomy group and palliative gastrectomy group. Propensity score matching (PSM) was performed to balance the selection bias. Results After 1:1 PSM, a total of 104 patients were included for final analysis. The median overall survival (OS) times in the gastrojejunostomy group and palliative gastrectomy group were 8.50 and 11.87 months, respectively (P = 0.243). The postoperative complication rates in the gastrojejunostomy group and palliative gastrectomy group were 19.23% (10/52) and 17.31% (9/52), respectively (P = 0.800), and no treatment-related death was observed. Multivariate analysis showed that periton0eal seeding (P = 0.014) and chemotherapy (P < 0.001) were independent prognostic factors. Among them, peritoneal seeding was a risk factor and postoperative chemotherapy was a protective factor. Conclusions Our results indicated that although the surgical complications of palliative gastrectomy were manageable, it showed no survival benefit. Therefore, relieving obstruction symptom, improving patients’ quality of life and creating better conditions for chemotherapy appear to be the main therapeutic strategies for advanced gastric cancer with GOO.

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β-Galactosidase is a target enzyme for detecting peritoneal metastasis of gastric cancer

Scientific Reports ◽

10.1038/s41598-021-88982-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hidemasa Kubo ◽

Yasutoshi Murayama ◽

Soichiro Ogawa ◽

Tatsuya Matsumoto ◽

Masayuki Yubakami ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Lines ◽

Peritoneal Metastasis ◽

Therapeutic Strategies ◽

Fluorescence Probes ◽

Gamma Glutamyl Transpeptidase ◽

Key Enzyme ◽

High Fluorescence ◽

Glutamyl Transpeptidase ◽

Target Enzyme

AbstractDiagnosis of peritoneal metastasis in gastric cancer (GC) is essential for determining appropriate therapeutic strategies and avoiding non-essential laparotomy or gastrectomy. Recently, a variety of activatable fluorescence probes that can detect enzyme activities have been developed for cancer imaging. The aim of this study was to identify the key enzyme involved in peritoneal metastasis in GC. The enzymatic activity of gamma-glutamyl transpeptidase, dipeptidyl peptidase IV, and β-galactosidase (β-Gal) was assessed in lysates prepared from preserved human GC (n = 89) and normal peritoneal (NP; n = 20) samples. β-Gal activity was significantly higher in the human GC samples than in NP samples, whereas no differences were observed in the activities of the other enzymes. Therefore, we used SPiDER-βGal, a fluorescent probe that can be activated by β-Gal, for imaging GC cell lines, peritoneal metastasis in a mouse model, and fresh human resected GC samples (n = 13). All cell lines showed fluorescence after applying SPiDER-βGal, and metastatic nodules in the mice gradually developed high fluorescence that could be visualized with SPiDER-βGal. The human GC samples showed significantly higher fluorescence than NP samples. β-Gal is a useful target enzyme for fluorescence imaging of peritoneal metastasis in GC.

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Variation in Gene Expression Patterns in Human Gastric Cancers

Molecular Biology of the Cell ◽

10.1091/mbc.e02-12-0833 ◽

2003 ◽

Vol 14 (8) ◽

pp. 3208-3215 ◽

Cited By ~ 197

Author(s):

Xin Chen ◽

Suet Y. Leung ◽

Siu T. Yuen ◽

Kent-Man Chu ◽

Jiafu Ji ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Patient Survival ◽

Expression Patterns ◽

Therapeutic Strategies ◽

Gene Expression Patterns ◽

Intrinsic Properties ◽

Normal Cells ◽

Common Cause ◽

Gastric Cancers

Gastric cancer is the world's second most common cause of cancer death. We analyzed gene expression patterns in 90 primary gastric cancers, 14 metastatic gastric cancers, and 22 nonneoplastic gastric tissues, using cDNA microarrays representing ∼30,300 genes. Gastric cancers were distinguished from nonneoplastic gastric tissues by characteristic differences in their gene expression patterns. We found a diversity of gene expression patterns in gastric cancer, reflecting variation in intrinsic properties of tumor and normal cells and variation in the cellular composition of these complex tissues. We identified several genes whose expression levels were significantly correlated with patient survival. The variations in gene expression patterns among cancers in different patients suggest differences in pathogenetic pathways and potential therapeutic strategies.

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