Abstract:
:HER2-directed therapies, such as trastuzumab and lapatinib, are important treatments for breast cancer. However, some tumors do not respond or develop resistance to these agents. We isolated and characterized multiple lapatinib-resistant, HER2-positive, estrogen receptor (ER)-positive breast cancer clones derived from lapatinib-sensitive BT474 cells by chronic exposure to lapatinib. We show overexpression of AXL as a novel mechanism of acquired resistance to HER2-targeted agents in these models. GSK1363089 (foretinib), a multikinase inhibitor of AXL, MET, and vascular endothelial growth factor receptor currently in phase II clinical trials, restores lapatinib and trastuzumab sensitivity in these resistant cells that exhibit increased AXL expression. Furthermore, small interfering RNA to AXL, estrogen deprivation, or fulvestrant, an ER antagonist, decreases AXL expression and restores sensitivity to lapatinib in these cells. Taken together, these data provide scientific evidence to assess the expression of AXL in HER2-positive, ER-positive patients who have progressed on either lapatinib or trastuzumab and to test the combination of HER2-targeted agents and GSK1363089 in the clinic.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Liu L,Greger J,Shi H,Liu Y,Greshock J,Annan R,Halsey W,Sathe GM,Martin AM,Gilmer TMdoi
10.1158/0008-5472.CAN-08-4490subject
Has Abstractpub_date
2009-09-01 00:00:00pages
6871-8issue
17eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-08-4490journal_volume
69pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Dysregulated signal transduction from receptor tyrosine kinases to phosphatidylinositol 3-kinase (PI3K), AKT (protein kinase B), and its effector FKBP-rapamycin-associated protein (FRAP) occurs via autocrine stimulation or inactivation of the tumor suppressor PTEN in many cancers. Here we demonstrate that in human pro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-03-15 00:00:00
abstract::Methotrexate (MTX) is one of the most commonly used agents in the treatment of solid malignancies; however, the toxicities of MTX to bone marrow and gastrointestinal tract complicate this therapy. We, therefore, propose a gene-dependent enzyme prodrug therapy to limit these toxicities by localizing the production of M...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::EphA2 receptor tyrosine kinase is frequently overexpressed in different human cancers, suggesting that it may promote tumor development and progression. However, evidence also exists that EphA2 may possess antitumorigenic properties, raising a critical question on the role of EphA2 kinase in tumorigenesis in vivo. We ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-0004
更新日期:2006-07-15 00:00:00
abstract::The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen in adult laboratory rodents. Our previous studies have shown that NNK crosses the placenta in pregnant hamsters and is metabolized into DNA-methylating and clastogenic intermediates by fetal respiratory tract t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Neuroblastomas often undergo spontaneous differentiation and/or regression in vivo, which is at least partly regulated by the signals through neurotrophins and their receptors. Recently, glial cell line-derived neurotrophic factor (GDNF) and a second family member, neurturin (NTN), have been found to mediate their sig...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-15 00:00:00
abstract::Mutations in the p53 tumor suppressor gene have been demonstrated to be one of the most frequent genetic abnormalities in human cancers. Previous studies have shown that the frequency of p53 mutations is significantly higher in small cell lung cancer than in non-small cell lung cancer. However, this conclusion was bas...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-11-15 00:00:00
abstract::Prostate cancer stem-like cells (PCSLC) are believed to be responsible for prostate cancer onset and metastasis. Autocrine and microenvironmental signals dictate PCSLC behavior and patient outcome. In prostate cancer patients, IL30/IL27p28 has been linked with tumor progression, but the mechanisms underlying this link...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-3117
更新日期:2018-05-15 00:00:00
abstract::The objective of this study was to compare the relative in vitro cytotoxicity of bleomycin to that of two newer-generation analogues, tallysomycin S10b and liblomycin. The latter compound is of particular interest as it has recently been shown in preclinical studies to be free of a potential to cause pulmonary injury ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Although aberrant microRNA (miRNA) is expressed in different types of human cancer tissues, its pathophysiologic role and the relevance of tumorigenesis and metastasis are still largely unknown. Here, we defined miRNAs involved in cancer metastasis (metastamirs) using an established mouse model for peritoneal dissemin...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2530
更新日期:2011-02-15 00:00:00
abstract::The possibility that neoplastic transformation may characteristically alter cell surface morphology prompted a comparison by scanning electron microscopy of nonneoplastic and tumorigenic cell lines from a single clone of mouse embryo cells. Among those studied by scanning electron microscopy, six lines of this clone p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::Plasmin is shown to play a crucial role in many pathophysiologic processes primarily through its ability to degrade extracellular matrix (ECM) and/or mobilizing growth factors that are sequestered in the ECM. Cysteine-rich 61 (CCN1) is a matricellular protein of which expression is up-regulated in cancer and various v...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0982
更新日期:2005-11-01 00:00:00
abstract::Cell division is essential for tumor development and progression. Methylation-mediated silencing caused by aberrant de novo methylation of CpG islands located in the promoter regions of growth regulatory genes occurs frequently in human cancers. We investigated the relationship between cell division and de novo methyl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-04-15 00:00:00
abstract::While more than 70% of breast cancers express estrogen receptor-α (ER+), endocrine therapies targeting these receptors often fail. The molecular mechanisms that underlie treatment resistance remain unclear. We investigated the potential role of glucose-regulated protein 78 (GRP78) in mediating estrogen resistance. Hum...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-0269
更新日期:2012-07-01 00:00:00
abstract::Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers....
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-0168
更新日期:2006-04-01 00:00:00
abstract::The aim of this study was to evaluate the promoter methylation status and loss of heterozygosity (LOH) of the SEMA3B in non-small cell lung cancers (NSCLCs). We analyzed the methylation status of semaphorin 3B (SEMA3B) promoter and LOH at 3p21.3 in eight NSCLC cell lines and 27 primary tumors. Hypermethylation of SEMA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-06-15 00:00:00
abstract::Extramedullary myelopoiesis occurs commonly in tumor-bearing animals and is known to lead to accumulation of peripheral myeloid-derived suppressor cells (MDSC), which play an important role in immune escape. However, the cellular and molecular mechanisms by which tumors induce extramedullary myelopoiesis are poorly un...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-1482
更新日期:2014-11-15 00:00:00
abstract::The effect(s) of treadmill exercise and type and amount of dietary fat on the process of mammary tumorigenesis was investigated. Female Sprague-Dawley rats were fed a purified 5% fat diet (AIN-76A) from 21 to 64 days of age. At 50 days of age each rat was intubated p.o. with 5 mg 7,12-dimethylbenz(a)anthracene (DMBA)....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-04-15 00:00:00
abstract::Sporadic prostate carcinoma is the most common male cancer in the Western world, yet many of the major genetic events involved in the progression of this often fatal cancer remain to be elucidated. Numerous cytogenetic and allelotype studies have reported frequent loss of heterozygosity on chromosomal arm 10q in spora...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-11-15 00:00:00
abstract::CI-921, an analogue of amsacrine with superior activity against in vivo and in vitro experimental tumor models, has been studied in 16 patients with solid tumors refractory to chemotherapy or for which conventional therapy does not exist. Thirty-nine cycles were given and doses escalated from 39 to 810 mg/m2. This tot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-15 00:00:00
abstract::There is a paucity of data on whether or not women can be reinfected with human papillomavirus (HPV) types to which they were exposed to earlier in life and on the role of natural immunity. The observation of HPV infection at older ages may be explained by the reactivation of a latent infection or new exposure from se...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0621
更新日期:2010-11-01 00:00:00
abstract::The radionuclide of choice for use in diagnosis in most nuclear medicine diagnostic procedures is 99mTc. It is important, therefore, to establish whether there is potential clinical efficacy of an antitumor antigen directed monoclonal antibody labeled with 99mTc. We have investigated the potential use of a 99mTc label...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::Epigenetic alterations of the genome such as DNA promoter methylation and chromatin remodeling play an important role in tumorigenesis. These modifications take place throughout development with subsequent events occurring later in adulthood. Recent studies, however, suggest that some epigenetic alterations that influ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-08-2184
更新日期:2008-11-15 00:00:00
abstract::Nervous system tumors represent unique neoplasms that arise within the central and peripheral nervous system. Recent progress in generating genetically engineered mouse models of these tumors has advanced our understanding of the critical molecular and cellular events important for the development of these tumors. Rec...
journal_title:Cancer research
pub_type:
doi:
更新日期:2003-06-01 00:00:00
abstract::Antigenic stimulation of athymic mice on the BALB/c background by infection with the pinworms Aspiculuris tetraptera and Syphacia obvelata or by xenografts of human tumors induced a proliferation of T- and B-lymphocytes in spleen and lymph nodes and occasional germinal center formation. The proliferating T-lymphocytes...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::In order to improve local control of tumors over that achievable with local hyperthermia and radiation, we are testing the use of systemic cis-diamminedichloroplatinum(II) (CDDP) in conjunction with the other two modalities. In the FSaIIC fibrosarcoma, growth delay experiments indicated that the use of any two modalit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-05-15 00:00:00
abstract::XRCC1 is a key component of DNA base excision repair, single strand break repair, and backup nonhomologous end-joining pathway. XRCC1 (X-ray repair cross-complementing gene 1) deficiency promotes genomic instability, increases cancer risk, and may have clinical application in breast cancer. We investigated XRCC1 expre...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-2929
更新日期:2013-03-01 00:00:00
abstract::Aneuploidy is invariably associated with poor proliferation of primary cells, but the specific contributions of abnormal karyotypes to cancer, a disease characterized by aneuploidy and dysregulated proliferation, remain unclear. In this study, I demonstrate that the transcriptional alterations caused by aneuploidy in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0749
更新日期:2013-11-01 00:00:00
abstract::3,4-Dihydro-2,2-dimethyl-2H-naptho[1,2,-b]pyran-5,6-dione (beta-lapachone) is a novel DNA repair inhibitor. It was tested for synergistic X-ray-induced lethality in combination with several halogenated pyrimidine radiosensitizers. Logarithmic-phase growing human epidermoid laryngeal carcinoma (HEp-2) cells were allowe...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-10-15 00:00:00
abstract::An assay using a bimane derivative has been developed to detect free glutathione (GSH) in individual viable cells by flow cytometry. Monochlorobimane [syn-(ClCH2CH3)-1,5-diazabicycla[3.30]acta-3,6-diene-2,8-dio ne], itself nonfluorescent, reacts with GSH to form a highly fluorescent derivative. High pressure liquid ch...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::The effect of hydrocortisone on blood-borne tumor metastasis was studied in an i.v. inoculation experiment with Ehrlich hypotetraploid clone 1, Ehrlich hypotetraploid stock, and Ehrlich hyperdiploid stock tumors. The administration of hydrocortisone before tumor inoculation resulted in increased tumor take, reduced me...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-04-01 00:00:00