Signal therapy of human pancreatic cancer and NF1-deficient breast cancer xenograft in mice by a combination of PP1 and GL-2003, anti-PAK1 drugs (Tyr-kinase inhibitors)

2007 ◽  
Vol 245 (1-2) ◽  
pp. 242-251 ◽  
Author(s):  
Yumiko Hirokawa ◽  
Alexander Levitzki ◽  
Guillaume Lessene ◽  
Jonathan Baell ◽  
Yi Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Kinase Inhibitors ◽  
Human Pancreatic Cancer ◽  
Breast Cancer Xenograft

scholarly journals SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Junjian Li ◽  
Xiaoliang Chen ◽  
Liqun Zhu ◽  
Zhenghong Lao ◽  
Tianhao Zhou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Tumor Stage ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Endogenous Expression ◽  
Egfr Tyrosine Kinase Inhibitors

AbstractPancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer mainly owing to its proclivity to early metastasis and the lack of effective targeted therapeutic drugs. Hence, understanding the molecular mechanisms underlying early invasion and metastasis by PDAC is imperative for improving patient outcomes. The present study identified that upregulation of TSPAN8 expression in PDAC facilitates metastasis in vivo and in vitro. We found SOX9 as a key transcriptional regulator of TSPAN8 expression in response to EGF stimulation. SOX9 modulation was sufficient to positively regulate endogenous expression of TSPAN8, with concomitant in vitro phenotypic changes such as loss of cell–matrix adherence and increased invasion. Moreover, increased SOX9 and TSPAN8 levels were shown to correlate in human pancreatic cancer specimens and downregulated in vitro by EGFR tyrosine kinase inhibitors. High expression of SOX9 and TSPAN8 has been associated with tumor stage, poor prognosis and poor patient survival in PDAC. In conclusion, this study highlights the importance of the EGF-SOX9-TSPAN8 signaling cascade in the control of PDAC invasion and implies that TSPAN8 may be a promising novel therapeutic target for the treatment of PDAC.

Tissue factor over-expression by human pancreatic cancer cells BXPC3 is related to higher prothrombotic potential as compared to breast cancer cells MCF7

2012 ◽  
Vol 129 (6) ◽  
pp. 779-786 ◽  
Author(s):  
Grigoris T. Gerotziafas ◽  
Vassiliki Galea ◽  
Elisabeth Mbemba ◽  
Amir Khaterchi ◽  
Mouna Sassi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Tissue Factor ◽  
Breast Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Over Expression ◽  
Pancreatic Cancer Cells

The efficacy of tyrosine kinase inhibitors on human pancreatic cancer cell lines1

2003 ◽  
Vol 115 (2) ◽  
pp. 219-225 ◽  
Author(s):  
Robert Saeid Farivar ◽  
James Gardner-Thorpe ◽  
Hiromichi Ito ◽  
Hassan Arshad ◽  
Michael J Zinner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Kinase Inhibitors ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell

In Vitro and In Vivo Antitumor Efficacy of Docetaxel and Sorafenib Combination in Human Pancreatic Cancer Cells

2010 ◽  
Vol 999 (999) ◽  
pp. 1-11
Author(s):  
P. Ulivi ◽  
C. Arienti ◽  
W. Zoli ◽  
M. Scarsella ◽  
S. Carloni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Antitumor Efficacy ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ilana Schlam ◽  
Sandra M. Swain
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Positive Breast Cancer

AbstractHuman epidermal growth factor receptor 2 (HER2) positive breast cancer accounts for 20–25% of all breast cancers. Multiple HER2-targeted therapies have been developed over the last few years, including the tyrosine kinase inhibitors (TKI) lapatinib, neratinib, tucatinib, and pyrotinib. These drugs target HER2 and other receptors of the epidermal growth factor receptor family, therefore each has unique efficacy and adverse event profile. HER2-directed TKIs have been studied in the early stage and advanced settings and have shown promising responses. There is increasing interest in utilizing these drugs in combination with chemotherapy and /or other HER2-directed agents in patients with central nervous system involvement, TKIs have shown to be effective in this setting for which treatment options have been previously limited and the prognosis remains poor. The aim of this review is to summarize currently approved TKIs for HER2+ breast, key clinical trials, and their use in current clinical practice.

scholarly journals NRG1 fusions in breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Karen D. Howarth ◽  
Tashfina Mirza ◽  
Susanna L. Cooke ◽  
Suet-Feung Chin ◽  
Jessica C. Pole ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Cancer Cell Line ◽  
Cytoplasmic Tail ◽  
Gene Fusions ◽  
Breast Cancers ◽  
Autocrine Loop ◽  
Multiple Transcripts ◽  
Autocrine Stimulation

Abstract Background NRG1 gene fusions may be clinically actionable, since cancers carrying the fusion transcripts can be sensitive to tyrosine kinase inhibitors. The NRG1 gene encodes ligands for the HER2(ERBB2)-ERBB3 heterodimeric receptor tyrosine kinase, and the gene fusions are thought to lead to autocrine stimulation of the receptor. The NRG1 fusion expressed in the breast cancer cell line MDA-MB-175 serves as a model example of such fusions, showing the proposed autocrine loop and exceptional drug sensitivity. However, its structure has not been properly characterised, its oncogenic activity has not been fully explained, and there is limited data on such fusions in breast cancer. Methods We analysed genomic rearrangements and transcripts of NRG1 in MDA-MB-175 and a panel of 571 breast cancers. Results We found that the MDA-MB-175 fusion—originally reported as a DOC4(TENM4)-NRG1 fusion, lacking the cytoplasmic tail of NRG1—is in reality a double fusion, PPP6R3-TENM4-NRG1, producing multiple transcripts, some of which include the cytoplasmic tail. We hypothesise that many NRG1 fusions may be oncogenic not for lacking the cytoplasmic domain but because they do not encode NRG1’s nuclear-localised form. The fusion in MDA-MB-175 is the result of a very complex genomic rearrangement, which we partially characterised, that creates additional expressed gene fusions, RSF1-TENM4, TPCN2-RSF1, and MRPL48-GAB2. We searched for NRG1 rearrangements in 571 breast cancers subjected to genome sequencing and transcriptome sequencing and found four cases (0.7%) with fusions, WRN-NRG1, FAM91A1-NRG1, ARHGEF39-NRG1, and ZNF704-NRG1, all splicing into NRG1 at the same exon as in MDA-MB-175. However, the WRN-NRG1 and ARHGEF39-NRG1 fusions were out of frame. We identified rearrangements of NRG1 in many more (8% of) cases that seemed more likely to inactivate than to create activating fusions, or whose outcome could not be predicted because they were complex, or both. This is not surprising because NRG1 can be pro-apoptotic and is inactivated in some breast cancers. Conclusions Our results highlight the complexity of rearrangements of NRG1 in breast cancers and confirm that some do not activate but inactivate. Careful interpretation of NRG1 rearrangements will therefore be necessary for appropriate patient management.

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