Abstract:
:Progression of prostate cancer has been associated with EGFR and HER2 activation and to tumor-initiating cells contribution toward chemotherapy resistance. We investigated the efficacy of a dual intervention against EGFR and HER2 to deplete the tumor-initiating cells, optimize the chemotherapy management and prevent the progression of castration-resistant prostate cancer (CRPC) cells. Using DU145, PC3, and 22Rv1 CRPC cell lines, biochemical analysis revealed activation of EGFR, HER2, MAPK, and STAT3 in DU145 and 22Rv1, and AKT and SRC in DU145 and PC-3. pSTAT3 nuclear staining was observed in DU145 xenografts and in 12 out of 14 CRPC specimens. The in vivo dual targeting of ErbB receptors with Cetuximab and Trastuzumab combined with chemotherapy caused an effective antitumor response in DU145 xenografted mice displaying STAT3 activation; conversely PC-3 bearing mice experienced tumor relapse. The potentiating of in vivo cytotoxic effect in DU145 model was accompanied by a significant decrease of prostatosphere-forming capacity assessed in vitro on residual tumor cells. Additionally, combined treatment in vitro with Cetuximab, Trastuzumab and chemotherapy negatively affected DU145 and 22Rv1 sphere formation, suggesting the critical function of ErbB receptors for tumor-initiating cells proliferation; no effect on PC-3 clonogenic potential was observed, indicating that other receptors than EGFR and HER2 may sustain PC3 tumor-initiating cells. These findings provided the preclinical evidence that the dual inhibition of EGFR and HER2 by targeting tumor-initiating cells may improve the efficacy of the current chemotherapy regimen, bringing benefits especially to castration-resistant patients with activated STAT3, and preventing disease progression.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Rossini A,Giussani M,Ripamonti F,Aiello P,Regondi V,Balsari A,Triulzi T,Tagliabue Edoi
10.1080/15384047.2020.1727702subject
Has Abstractpub_date
2020-05-03 00:00:00pages
463-475issue
5eissn
1538-4047issn
1555-8576journal_volume
21pub_type
杂志文章abstract::Heparan sulfate proteoglycans (HSPGs) play important roles in cancer initiation and progression, by interacting with the signaling pathways that affect proliferation, adhesion, invasion and angiogenesis. These roles suggest the possibility of various strategies of regulation of these molecules. In this review, we demo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1838034
更新日期:2020-12-01 00:00:00
abstract::Telomerase is the ribonucleoprotein that enables cancer and stem cells to maintain their telomeres, resulting in unlimited proliferative potential. The catalytic component of telomerase in humans, hTERT, is upregulated in nearly 90% of all cancers, making it the most widely expressed marker of malignancy. With the exc...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.2.2.255
更新日期:2003-03-01 00:00:00
abstract::Breast cancer is one of the most commonly diagnosed malignancies in women. Despite the remarkable success of mammography screening and use of adjuvant systemic therapy, it is estimated that approximately 200,000 new diagnoses will be made this year and 40,000 deaths will occur due to this disease (American Cancer Soci...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.9.17677
更新日期:2011-11-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26106
更新日期:2013-11-01 00:00:00
abstract:PURPOSE:Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme, plays an important role in immune escape through suppressing T-cell function. Since Vav1 signaling pathway regulates T cell homeostasis, this study was designed to test the hypothesis that IDO induces T-cell immunosuppression through inhibiting V...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.14.8882
更新日期:2009-07-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.27821
更新日期:2014-04-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2019.1595283
更新日期:2019-01-01 00:00:00
abstract::Cancer-testis antigens (CTAs) are often specifically expressed in cancer cells and under normal conditions are only considered to be expressed in the germ line cells and the placenta. CTAs are potential targets for cancer immunotherapy and therefore necessitates their expression profiling. The expression profile of LA...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.3.15949
更新日期:2011-08-01 00:00:00
abstract::Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.6.1734
更新日期:2005-06-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20562
更新日期:2012-07-01 00:00:00
abstract::We studied the mechanism of the cytotoxic activity of BZL101, an aqueous extract from the herb Scutellaria barbata D. Don, which is currently in phase II clinical trial in patients with advanced breast cancer. The phase I trial showed favorable toxicity profile and promising efficacy. We report here that BZL101 induce...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.4.5535
更新日期:2008-04-01 00:00:00
abstract::The Forkhead Box transcription factor FoxM1 regulates expression of genes that promote cell cycle progression, and it plays essential roles in the development of liver, lung, prostate and colorectal tumors. Thiazolidinediones (TZDs) activate the peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activa...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.12.11710
更新日期:2010-06-15 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20834
更新日期:2012-08-01 00:00:00
abstract::The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is important in nasopharyngeal carcinoma (NPC) pathogenesis. Activated PI3K and its downstream target Akt are concernful signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis and oncogenesis. The protein kinase A...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.4.7433
更新日期:2009-02-01 00:00:00
abstract::Oral squamous cell carcinoma (OSCC), the subtype of head and neck cancers, is notorious for its high incidence and death rate. The role of long non-coding RNAs (lncRNAs) is discovered to be significant for the canceration and cancer progression. Long intergenic non-protein coding RNA 958 (LINC00958) is discovered as a...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1617571
更新日期:2019-01-01 00:00:00
abstract::Ten years ago, a concerted effort from several labs resulted in the cloning of BRCA1, the first of two major hereditary breast/ovarian cancer predisposition genes. Since that time, BRCA1 has been linked to several key nuclear functions connected with the prevention of genomic instability. In particular, BRCA1 function...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.3.6.842
更新日期:2004-06-01 00:00:00
abstract::Polo-like kinase 1 (Plk1) is a key cell cycle regulator that is frequently overexpressed in human hepatocellular carcinomas. Blockade of the Plk1 pathway has been reported to be capable of inducing anti-tumor effect. Here, plasmids containing U6 promoter-driven shRNAs against human Plk1 were constructed and transfecte...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.4.14178
更新日期:2011-02-15 00:00:00
abstract:INTRODUCTION:Malignant cells are capable of an unlimited number of cell divisions, either through production of telomerase, or through the alternate lengthening of telomere (ALT) mechanism. Yeast cells with genomic instability have been shown to survive in the absence of telomerase by increased recombination events. We...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.12.1235
更新日期:2004-12-01 00:00:00
abstract::Traditionally, estrogen signaling was thought to be mediated strictly through genomic pathways. Recently, however, it has been demonstrated that estrogen stimulation of cells leads to rapid nongenomic effects including ERK activation. While the precise mechanism of this action is still under investigation, it is known...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.12.3378
更新日期:2006-12-01 00:00:00
abstract::Methylthioadenosine phosphorylase (MTAP), a key enzyme in the catabolism of 5'-deoxy-5'-methylthioadenosine (MTA), catalyzes the formation of adenine and 5-methylthioribose-1-phosphate. MTAP is expressed in all cells throughout the body, but a significant percentage of human tumors have lost MTAP expression, thereby m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.21115
更新日期:2012-09-01 00:00:00
abstract::Antitumor imidazoacridinone C-1311 is a DNA-reactive topoisomerase II and FLT3 receptor tyrosine kinase inhibitor. Here, we demonstrate the mechanism of C-1311 inhibitory action on novel targets: hypoxia-inducible factor-1α (HIF-1α), vascular-endothelial growth factor (VEGF), and angiogenesis. In a cell-free system, C...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2011-10-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.12.1223
更新日期:2004-12-01 00:00:00
abstract::Recent reports have shown that cancer stem cells exist in many malignancies. Side population (SP) cells are used to enrich cancer stem-like cells in many cell lines and fresh tumor specimens. In this study, we cultured primary esophageal squamous cell carcinoma (ESCC) cells from ESCC tissue specimens. SP cells from pr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.11.15531
更新日期:2011-06-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.1.12162
更新日期:2010-07-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1529122
更新日期:2019-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.22.9687
更新日期:2009-11-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00
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journal_title:Cancer biology & therapy
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更新日期:2006-02-01 00:00:00
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journal_title:Cancer biology & therapy
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doi:10.1080/15384047.2015.1071730
更新日期:2015-01-01 00:00:00
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journal_title:Cancer biology & therapy
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