Anti-EGFR therapeutic efficacy correlates directly with inhibition of STAT3 activity.

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 Ther

journal_title

Cancer biology & therapy

authors

Ung N,Putoczki TL,Stylli SS,Ng I,Mariadason JM,Chan TA,Zhu HJ,Luwor RB

doi

10.4161/cbt.28179

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

623-32

issue

5

eissn

1538-4047

issn

1555-8576

pii

28179

journal_volume

15

pub_type

杂志文章
  • APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q.

    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

    authors: Arnold CN,Goel A,Niedzwiecki D,Dowell JM,Wasserman L,Compton C,Mayer RJ,Bertagnolli MM,Boland CR

    更新日期:2004-10-01 00:00:00

  • In vivo long-term imaging and radioiodine therapy by sodium-iodide symporter gene expression using a lentiviral system containing ubiquitin C promoter.

    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

    authors: Kim HJ,Jeon YH,Kang JH,Lee YJ,Kim KI,Chung HK,Jeong JM,Lee DS,Lee MC,Chung JK

    更新日期:2007-07-01 00:00:00

  • Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib.

    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

    authors: Lou E,Schomaker M,Wilson JD,Ahrens M,Dolan M,Nelson AC

    更新日期:2016-10-02 00:00:00

  • Combined endostatin and TRAIL gene transfer suppresses human hepatocellular carcinoma growth and angiogenesis in nude mice.

    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

    authors: Zhang Y,Qu ZH,Cui M,Guo C,Zhang XM,Ma CH,Sun WS

    更新日期:2009-03-01 00:00:00

  • ETS-TMPRSS2 fusion gene products in prostate cancer.

    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

    authors: Ahlers CM,Figg WD

    更新日期:2006-03-01 00:00:00

  • CIP2A expression and localization in oral carcinoma and dysplasia.

    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

    authors: Katz J,Jakymiw A,Ducksworth MK,Stewart CM,Bhattacharyya I,Cha S,Chan EK

    更新日期:2010-10-01 00:00:00

  • Pyoluteorin derivatives induce Mcl-1 degradation and apoptosis in hematological cancer cells.

    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

    authors: Doi K,Gowda K,Liu Q,Lin JM,Sung SS,Dower C,Claxton D,Loughran TP Jr,Amin S,Wang HG

    更新日期:2014-01-01 00:00:00

  • Retinoid-induced growth arrest of breast carcinoma cells involves co-activation of multiple growth-inhibitory genes.

    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

    authors: Dokmanovic M,Chang BD,Fang J,Roninson IB

    更新日期:2002-01-01 00:00:00

  • Managing bone complications of solid tumors.

    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

    authors: Berenson JR,Rajdev L,Broder M

    更新日期:2006-09-01 00:00:00

  • Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression.

    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

    authors: VanOosten RL,Moore JM,Karacay B,Griffith TS

    更新日期:2005-10-01 00:00:00

  • Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients.

    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

    authors: Mourad L,El-Ahwany E,Zoheiry M,Abu-Taleb H,Hassan M,Ouf A,Rahim AA,Hassanien M,Zada S

    更新日期:2018-05-04 00:00:00

  • β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells.

    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

    authors: Wilson JM,Lorimer E,Tyburski MD,Williams CL

    更新日期:2015-01-01 00:00:00

  • C7 peptide inhibits hepatocellular carcinoma metastasis by targeting the HGF/c-Met signaling pathway.

    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

    authors: Zhao M,Wang Y,Liu Y,Zhang W,Liu Y,Yang X,Cao Y,Wang S

    更新日期:2019-01-01 00:00:00

  • Silencing the intestinal GUCY2C tumor suppressor axis requires APC loss of heterozygosity.

    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

    authors: Pattison AM,Barton JR,Entezari AA,Zalewski A,Rappaport JA,Snook AE,Waldman SA

    更新日期:2020-09-01 00:00:00

  • BRCA1 phosphorylation: biological consequences.

    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

    authors: Ouchi T

    更新日期:2006-05-01 00:00:00

  • FBXO4 loss facilitates carcinogen induced papilloma development in mice.

    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

    authors: Lian Z,Lee EK,Bass AJ,Wong KK,Klein-Szanto AJ,Rustgi AK,Diehl JA

    更新日期:2015-01-01 00:00:00

  • DNA methylation regulates MicroRNA expression.

    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

    authors: Han L,Witmer PD,Casey E,Valle D,Sukumar S

    更新日期:2007-08-01 00:00:00

  • Triggering of toll-like receptor-4 in human multiple myeloma cells promotes proliferation and alters cell responses to immune and chemotherapy drug attack.

    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

    authors: Bao H,Lu P,Li Y,Wang L,Li H,He D,Yang Y,Zhao Y,Yang L,Wang M,Yi Q,Cai Z

    更新日期:2011-01-01 00:00:00

  • The efficacy of lorlatinib in a lung adenocarcinoma patient with a novel ALK G1202L mutation: a case report.

    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

    authors: Meng Z,Li T,Wang P,Lizaso A,Huang D

    更新日期:2021-01-02 00:00:00

  • A LIN28B polymorphism predicts for colon cancer survival.

    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

    authors: Ye Y,Madison B,Wu X,Rustgi AK

    更新日期:2012-12-01 00:00:00

  • Increased gene copy number of the transcription factor E2F1 in malignant melanoma.

    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

    authors: Nelson MA,Reynolds SH,Rao UN,Goulet AC,Feng Y,Beas A,Honchak B,Averill J,Lowry DT,Senft JR,Jefferson AM,Johnson RC,Sargent LM

    更新日期:2006-04-01 00:00:00

  • A proposed clinical test for monitoring fluoropyrimidine therapy: detection and stability of thymidylate synthase ternary complexes.

    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

    authors: Brody JR,Gallmeier E,Yoshimura K,Hucl T,Kulesza P,Canto MI,Hruban RH,Schulick RD,Kern SE

    更新日期:2006-08-01 00:00:00

  • Knockdown of ezrin via RNA interference suppresses Helicobacter pylori-enhanced invasion of gastric cancer cells.

    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

    authors: Fan LL,Chen DF,Lan CH,Liu KY,Fang DC

    更新日期:2011-04-15 00:00:00

  • Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis.

    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

    authors: Habib SL,Danial E,Nath S,Schneider J,Jenkinson CP,Duggirala R,Abboud HE,Thameem F

    更新日期:2008-01-01 00:00:00

  • A targeted IL-15 fusion protein with potent anti-tumor activity.

    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

    authors: Chen S,Huang Q,Liu J,Xing J,Zhang N,Liu Y,Wang Z,Li Q

    更新日期:2015-01-01 00:00:00

  • Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis.

    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

    authors: Lee DJ,Schönleben F,Banuchi VE,Qiu W,Close LG,Assaad AM,Su GH

    更新日期:2010-10-01 00:00:00

  • MEK1/2 inhibition promotes Taxotere lethality in mammary tumors in vivo.

    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

    authors: Yacoub A,Gilfor D,Hawkins W,Park MA,Hanna D,Hagan MP,Curiel DT,Fisher PB,Grant S,Dent P

    更新日期:2006-10-01 00:00:00

  • Enhanced acute apoptotic response to azoxymethane-induced DNA damage in the rodent colonic epithelium by Tyrian purple precursors: a potential colorectal cancer chemopreventative.

    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

    authors: Westley CB,McIver CM,Abbott CA,Le Leu RK,Benkendorff K

    更新日期:2010-03-01 00:00:00

  • Combined targeting of EGFR and HER2 against prostate cancer stem cells.

    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

    authors: Rossini A,Giussani M,Ripamonti F,Aiello P,Regondi V,Balsari A,Triulzi T,Tagliabue E

    更新日期:2020-05-03 00:00:00

  • Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line.

    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

    authors: Qi L,Singh RP,Lu Y,Agarwal R,Harrison GS,Franzusoff A,Glode LM

    更新日期:2003-09-01 00:00:00