Abstract:
:Several agents targeting the epidermal growth factor receptor (EGFR) have been FDA-approved to treat cancer patients with varying tumor types including metastatic colorectal cancer. Many patients treated with anti-EGFR therapy however do not respond and those that do initially respond often acquire resistance. Here we show a clear correlation between the efficacy of anti-EGFR inhibitors with their ability to inhibit STAT3 activity in A431 epidermoid carcinoma cells and in a series of wt K-RAS expressing human colon cancer cell lines. Furthermore, the ability of cetuximab to inhibit growth also correlated with its ability to inhibit STAT3 activity in tumor xenograft animal studies. In addition, stable knockdown of the STAT3 phosphatase, protein tyrosine phosphatase receptor delta (PTPRD) resulted in enhanced STAT3 activity and subsequent resistance to cetuximab in DIFI colon carcinoma cells. This resistance could be reversed by STAT3 inhibition. Finally, HN5 cells with acquired resistance to the EGFR tyrosine kinase inhibitor, AG1478 displayed greater STAT3 activity than the HN5 control cell line. These AG1478-refractory HN5 cells were re-sensitized to AG1478, cetuximab and erlotinib when co-treated with a STAT3 inhibitor. Taken together, our current data indicates a key role of STAT3 activity in promoting resistance to anti-EGFR therapy and suggests that anti-EGFR therapy in combination with inhibitors that block STAT3 may provide therapeutic benefit for patients with mCRC and other EGFR driven tumor types.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Ung N,Putoczki TL,Stylli SS,Ng I,Mariadason JM,Chan TA,Zhu HJ,Luwor RBdoi
10.4161/cbt.28179subject
Has Abstractpub_date
2014-05-01 00:00:00pages
623-32issue
5eissn
1538-4047issn
1555-8576pii
28179journal_volume
15pub_type
杂志文章abstract:INTRODUCTION:Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. However, to abrogate APC function, both alleles must be inactivated. Recently, it has been demonstrated that epigenetic modification of the APC promo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.10.1113
更新日期:2004-10-01 00:00:00
abstract::To establish stable and long-term gene expression in vitro and in vivo, we developed a lentiviral vector system carrying sodium iodide symporter (hNIS) gene under UbC promoter, and transfected this into a colon cancer cell line. The in vitro and in vivo kinetics of radioiodine and [99mTc]-pertechnetate were then inves...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.7.4342
更新日期:2007-07-01 00:00:00
abstract::Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (no...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1220453
更新日期:2016-10-02 00:00:00
abstract::Endostatin can inhibit tumor growth by blocking angiogenesis, whereas tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill cancer cells without toxicity to most normal cells. To establish the combined anti-tumor therapeutic effect of endostatin and solu...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.5.7687
更新日期:2009-03-01 00:00:00
abstract::Genes playing a role in carcinogenesis have often been identified through analysis of recurrent chromosomal rearrangements. Although such rearrangements are well known in leukemias, lymphomas, and sarcomas, they have not been well characterized in carcinomas. In the October 28, 2005 issue of Science, a study by Tomlin...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.3.2603
更新日期:2006-03-01 00:00:00
abstract:AIMS:Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity resulting in severe morbidity and mortality. To date only few proteins have been suggested as potential biomarkers or targets for this type of cancer. Cancerous inhibitor of PP2A (CIP2A) is a protein expressed in epithelial tis...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.10.7.12895
更新日期:2010-10-01 00:00:00
abstract::Mcl-1, a pro-survival member of the Bcl-2 protein family, is an attractive target for cancer therapy. We have recently identified the natural product marinopyrrole A (maritoclax) as a novel small molecule Mcl-1 inhibitor. Here, we describe the structure-activity relationship study of pyoluteorin derivatives based on m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972799
更新日期:2014-01-01 00:00:00
abstract::Retinoids are used in leukemia therapy and chemoprevention of cancers. Treatment of MCF-7 breast carcinoma cells with low doses of retinoids induces gradual proliferation arrest with phenotypic markers of senescence. cDNA microarray hybridization and reverse transcription-polymerase chain reaction analysis showed that...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.1.1.35
更新日期:2002-01-01 00:00:00
abstract::Bone metastases are a common occurrence in patients with breast cancer, lung cancer and prostate cancer. Bone metastases cause considerable morbidity including pain, impaired mobility, pathologic fracture, spinal cord or nerve root compression, bone marrow infiltration and hypercalcemia of malignancy. These complicati...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.9.3308
更新日期:2006-09-01 00:00:00
abstract::Every year, 12,000 people in the U.S. die from renal cell carcinoma. Current therapies include partial or complete nephrectomy or treatments such as administration of IFN-alpha and/or interleukins that are moderately effective, at best. Moreover, the current therapies are invasive and inefficient and new therapies are...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.10.2022
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVES:Due to the absence of reliable and accurate biomarkers for the early detection of liver malignancy, circulating microRNAs have recently emerged as great candidates for prompt cancer identification. Therefore, the aim of this study was to investigate the potential of liver-specific circulating microRNAs as an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1423922
更新日期:2018-05-04 00:00:00
abstract::A greater understanding of the molecular basis of breast cancer metastasis will lead to identification of novel therapeutic targets and better treatments. Rap1B is a small GTPase that suppresses the metastasis of breast cancer cells by increasing cell-cell adhesion. In breast cancer, a decrease in Rap1B prenylation an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1070988
更新日期:2015-01-01 00:00:00
abstract::Hepatocellular carcinoma (HCC), characterized by a high rate of metastasis and recurrence after surgery, is caused by malignant proliferation of hepatocytes with epigenetic and/or genetic mutations. In particular, abnormal activation of the hepatocyte growth factor (HGF)-/c-mesenchymal-epithelial transition receptor (...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1647051
更新日期:2019-01-01 00:00:00
abstract::Most sporadic colorectal cancer reflects acquired mutations in the adenomatous polyposis coli (APC) tumor suppressor gene, while germline heterozygosity for mutant APC produces the autosomal dominant disorder Familial Adenomatous Polyposis (FAP) with a predisposition to colorectal cancer. In these syndromes, loss of h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1779005
更新日期:2020-09-01 00:00:00
abstract::More than a decade has passed since BRCA1, breast cancer tumor suppressor 1, was isolated by reverse genetics in 1994. Its molecular structure and potential function have been extensively studied; both mouse genetics and a cell culture system revealed that BRCA1 is a 220,240 kD nuclear phosphoprotein, it regulates tra...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.5.2845
更新日期:2006-05-01 00:00:00
abstract::Cyclin D1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC) and is considered a key driver of this disease. Mutations in FBXO4, F-box specificity factor that directs SCF-mediated ubiquitylation of cyclin D1, occur in ESCC with concurrent overexpression of cyclin D1 suggesting a potential tumor s...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1026512
更新日期:2015-01-01 00:00:00
abstract::MicroRNAs (miRNAs), an important class of small regulatory molecules for gene expression, are transcribed by RNA polymerase II. But little is known about the mechanisms that control miRNA expression. Comparing miRNA expression profiles between colon cancer cell line HCT 116 and its derivative, DNA methyltransferase 1 ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.8.4486
更新日期:2007-08-01 00:00:00
abstract::Multiple myeloma (MM) is an incurable B-cell malignancy characterized by accumulation of malignant plasma cells in the bone marrow and by recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections. The aim of this study was to investigate TLR initiated responses...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.1.13878
更新日期:2011-01-01 00:00:00
abstract::Acquired mutations in anaplastic lymphoma kinase (ALK) gene have been implicated as the major resistance mechanism to ALK inhibitors; however, information on the treatment options after acquiring novel ALK secondary mutations is limited. Herein, we report the efficacy of lorlatinib upon the detection of a novel ALK G1...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1836947
更新日期:2021-01-02 00:00:00
abstract::The pathogenesis of sporadic colorectal cancer involves distinct pathways, with characteristic genomic alterations. The first pathway, chromosome instability (CIN), is driven by APC mutations and is typified by Kras mutations, p53 mutation/loss of heterozygosity, and deletions at chromosome 18q. The second pathway is ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.22336
更新日期:2012-12-01 00:00:00
abstract::Translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. We have previously shown a unique translocation in malignant melanoma cells der(12)t(12;20). The transcription factor E2F1 maps to 20q11. Increased expression of E2F h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.4.2512
更新日期:2006-04-01 00:00:00
abstract::5-fluorouracil forms classic (covalent, ternary) complexes consisting of thymidylate synthase, fluoro-deoxyuridine monophosphate, and 5,10-methylene tetrahydrofolate. Despite a high pharmacologic interest in the classic complexes formed in cells treated with fluorouracil anticancer agents, the in vivo stability of the...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.8.2976
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND AND AIM:H. pylori interacts with gastric epithelial cells, which may activate signaling pathways important for gastric cancer invasion. Ezrin, a membrane cytoskeletal crosslinker protein, is well documented to regulate cell adhesion and cell motility. The aim of the present study was to determine whether ezr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.8.14691
更新日期:2011-04-15 00:00:00
abstract::The enzyme 8-oxoguanine glycosylase 1 (OGG1) repairs 8-oxo-2-deoxyguanosine residue (8-oxodG) an oxidatively damaged promutagenic base. Genetic variations in OGG1 gene have been shown to modulate DNA repair capacity and are related risk of tumor development. However, epidemiologic findings have been inconsistent. The ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.1.5120
更新日期:2008-01-01 00:00:00
abstract::IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071739
更新日期:2015-01-01 00:00:00
abstract::Head and neck squamous cell carcinoma (HNSCC) remains a significant cause of morbidity and mortality. There has been a great interest in finding specific genomic changes which contribute to HNSCC tumorigenesis, especially within the chromosome 3p area, where high frequency of LOH (loss of heterozygosity) has been repo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.7.12886
更新日期:2010-10-01 00:00:00
abstract::Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anti-cancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.10.3215
更新日期:2006-10-01 00:00:00
abstract::Colorectal cancer (CRC) is the second most prevalent and deadly cancer worldwide. Due to the mortality and morbidity associated with chemotherapeutic regimes, research is turning to natural product enhancement of the acute apoptotic response to genotoxic carcinogens (AARGC). Although Tyrian purple dye pigments and pre...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.5.10887
更新日期:2010-03-01 00:00:00
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 t...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1727702
更新日期:2020-05-03 00:00:00
abstract::Silibinin, derived from milk thistle extract, has been shown to inhibit growth factor receptor-mediated mitogenic and cell survival signaling, and to alter cell cycle regulators. Alteration in pathways regulating cell growth likely account for silibinin's inhibition of tumor growth. Since the epidermal growth factor r...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.5.452
更新日期:2003-09-01 00:00:00