Abstract：
BACKGROUND:Activated anaplastic lymphoma kinase (ALK) gene fusions are recurrent events in a small fraction of colorectal cancers (CRCs), although these events have not yet been exploited as in other malignancies. METHODS:We detected ALK protein expression by immunohistochemistry and gene rearrangements by fluorescence in situ hybridisation in the ALKA-372-001 phase I study of the pan-Trk, ROS1, and ALK inhibitor entrectinib. One out of 487 CRCs showed ALK positivity with a peculiar pattern that prompted further characterisation by targeted sequencing using anchored multiplex PCR. RESULTS:A novel ALK fusion with the carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) gene (CAD-ALK fusion gene) was identified. It resulted from inversion within chromosome 2 and the fusion of exons 1-35 of CAD with exons 20-29 of ALK. After failure of previous standard therapies, treatment of this patient with the ALK inhibitor entrectinib resulted in a durable objective tumour response. CONCLUSIONS:We describe the novel CAD-ALK rearrangement as an oncogene and provide the first evidence of its drugability as a new molecular target in CRC.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Amatu A,Somaschini A,Cerea G,Bosotti R,Valtorta E,Buonandi P,Marrapese G,Veronese S,Luo D,Hornby Z,Multani P,Murphy D,Shoemaker R,Lauricella C,Giannetta L,Maiolani M,Vanzulli A,Ardini E,Galvani A,Isacchi A,Sartoredoi
10.1038/bjc.2015.401subject
Has Abstractpub_date
2015-12-22 00:00:00pages
1730-4issue
12eissn
0007-0920issn
1532-1827pii
bjc2015401journal_volume
113pub_type
杂志文章abstract：:Experiments were conducted to determine whether bladder cancer would develop in primates (Papio sp.) infected with S. haematobium and concurrently exposed to low initiating doses of the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). To control for the systemic effects of schistosomiasis, 5 baboons wer...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1980.308
更新日期：1980-11-01 00:00:00
abstract：:To investigate whether parents of children with congenital malformations more often developed cancer after birth of the child, a population-based case-control study in Denmark was undertaken. By linking the Cancer Registry with the Central Population Registry, we identified 8783 cancer patients having their first chil...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600488
更新日期：2002-08-27 00:00:00
abstract：:Resistance of tumour cells to methylating and monochloroethylating agents in vitro and in vivo has been linked to levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In a clinical trial of temozolomide in advanced malignant melanoma, the relationship between pretreatment MGMT levels in biop...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1998.654
更新日期：1998-11-01 00:00:00
abstract：:We examined polymorphisms in exons 3 and 4 of microsomal epoxide hydrolase in 101 patients with colon cancer and compared the results with 203 control samples. The frequency of the exon 3 T to C mutation was higher in cancer patients than in controls (odds ratio 3.8; 95% confidence intervals 1.8-8.0). This sequence al...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690028
更新日期：1999-01-01 00:00:00
abstract：:Broad-spectrum neuropeptide growth factor antagonists, such as [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P (antagonist D) and [Arg6, D-Trp7,9, NmePhe8]substance P(6-11) (antagonist G), are currently being investigated as possible anti-tumour agents. These compounds are hoped to be effective against neuropeptide-drive...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.126
更新日期：1996-03-01 00:00:00
abstract：:Epstein-Barr virus (EBV) expression was investigated by immunohistochemistry (latent membrane protein 1 [LMP-1]) and in situ hybridization (EBV encoded RNA [EBER]) in biopsies from 95 patients with untreated Hodgkin's disease (HD). Tumour EBV status was related to EBV antibody titres, spontaneous and concanavalin A in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690827
更新日期：1999-12-01 00:00:00
abstract：:The development of resistance to vincristine, actinomycin D and cisplatin has been examined in a human epidermoid lung carcinoma xenograft line (HXL 55) growing in nude mice. Treatment of HXL 55 with 1 mg kg-1 vincristine or 0.5 mg kg-1 actinomycin D once in each in vivo passage resulted in a rapid reduction in tumour...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.155
更新日期：1988-07-01 00:00:00
abstract：:Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A. The analysis was intended to determine whether cyclin A has additional prognostic value for predicting patients' survival and drug response. Of the 187 NSCLCs,...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.302
更新日期：1997-01-01 00:00:00
abstract：:Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modifi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600708
更新日期：2003-01-13 00:00:00
abstract：:Over the period 1966-1995, based on 11,662 patients, the incidence of squamous cell carcinoma of the skin increased three to four times in Norway mainly as a result of an increased number of localized tumours. In men, cancer of the auricle was the second most common site; in women the incidence was low. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690725
更新日期：1999-10-01 00:00:00
abstract：BACKGROUND:Alternative treatments are needed for elderly patients with acute myeloid leukaemia, as the disease prognosis is poor and the current treatment is unsuitable for many patients. METHODS:In this study, we investigated whether combining the nucleoside analogue sapacitabine with histone deacetylase (HDAC) inhib...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605922
更新日期：2010-10-26 00:00:00
abstract：:Treatment failure in AML is often attributed to P-glycoprotein-associated multidrug resistance. However, the importance of increased DNA repair in resistant cells is becoming more apparent. In order to investigate the ability of the DNA repair inhibitor aphidicolin to modulate drug resistance, we continually exposed b...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1639
更新日期：2001-03-02 00:00:00
abstract：:Choriocarcinoma can be imaged by external scintigraphy after intravenous administration of radiolabelled antibody directed against human chorionic gonadotrophin (HCG). The purpose of this study was to investigate whether antibody imaging was sufficiently sensitive and specific to improve the selection of patients for ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.134
更新日期：1987-06-01 00:00:00
abstract：BACKGROUND:We evaluated systemic immune-inflammation index (SII) and its association with patient outcome in germ-cell tumours (GCTs). METHODS:Two independent cohorts of patients were analysed; the discovery set (n=171) from a single institution and the validation set (n=181) previously included in a study evaluating ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.460
更新日期：2018-03-20 00:00:00
abstract：BACKGROUND:We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. METHODS:We report the screening of an in-house drug library to id...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.83
更新日期：2014-03-18 00:00:00
abstract：:The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutatio...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1054/bjoc.2001.2128
更新日期：2001-12-14 00:00:00
abstract：:We investigated whether dietary intakes of total fat, monounsaturated fat (MUFA), polyunsaturated fat (PUFA) and saturated fat (SFA) were associated with breast cancer risk in a prospective cohort of 49 261 Swedish women (30-49 years at enrolment), which yielded 974 breast cancer cases by December 2005. Further, we ev...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604033
更新日期：2007-12-03 00:00:00
abstract：:To distinguish risk factors for acquisition of cervical human papillomavirus (HPV) infection from the determinants of neoplasia among infected individuals we have conducted a three-arm case-control study nested within a large population-based cohort of women (the Manchester cohort) screened for HPV at entry using L1 c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1523
更新日期：2000-12-01 00:00:00
abstract：BACKGROUND:Operable non-small cell lung cancer (NSCLC) patients whose tumours have spread to regional or central lymph nodes at the time of diagnosis have dismal prognoses compared with those who have limited disease. The current TNM staging system for NSCLC poorly distinguishes patients with lymph-node metastases who ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.92
更新日期：2016-05-10 00:00:00
abstract：:The sequential histological changes and neoplastic response occurring in the subcutaneous tissue of rats after injection of surfactants or carcinogens were compared. Twice weekly subcutaneous injections of the surfactants Blue VRS and Light Green SF elicited a deranged connective tissue repair with continued prolifera...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.28
更新日期：1973-03-01 00:00:00
abstract：BACKGROUND:Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS:Tumour samples from a phase III clinical trial of cetuximab plu...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.753
更新日期：2014-02-04 00:00:00
abstract：:The effects of cis-dichlorodiammine platinum II (DDP) on the intestinal mucosa and the kidney were studied after single and multiple treatments with intervals of 7-45 days. After a single treatment, the jejunal epithelium underwent a transient interruption of cell proliferation followed by a hyperplastic recovery and ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1982.45
更新日期：1982-02-01 00:00:00
abstract：:Androgen receptor (AR) signalling drives neoplastic growth and therapy resistance in prostate cancer. Recent clinical data show that docetaxel combined with androgen deprivation therapy improves outcome in hormone-sensitive disease. We studied whether testosterone and AR signalling interferes with docetaxel treatment ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-01105-y
更新日期：2020-12-01 00:00:00
abstract：:The origin of metastatic adenocarcinoma lesions can sometimes be difficult to diagnose. The objectives of our study were to establish the cytokeratin staining pattern of primary and metastatic lung and colorectal adenocarcinomas, and to determine if this helps to identify the site of origin of metastatic lesions. We r...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600326
更新日期：2002-06-17 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity: VEGFR-1/flt-1 and VEGFR-2/flk-1, which are expressed mainly in vascular endothelial cells. To the...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6692206
更新日期：1999-12-01 00:00:00
abstract：:Recent investigations have increasingly focussed attention on the roles of intracellular vesicle trafficking in the regulation of epithelial polarity and transformation. Rab25, an epithelial-specific member of the Rab family of small GTPases, has been associated with several epithelial cancers. Whereas Rab25 overexpre...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6605983
更新日期：2011-01-04 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in col...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1936
更新日期：2001-08-17 00:00:00
abstract：:Apoptosis plays an important role in tumorigenesis. Tumour growth is determined by the rate of cell proliferation and cell death. We counted the number of apoptotic cells in haematoxylin and eosin (H&E)-stained tumour sections in series of 172 grade I and II invasive breast cancers with long-term follow-up. The number...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.0928
更新日期：2000-01-01 00:00:00
abstract：:The use of cytotoxic drug vincristine (VCR) is limited by the occurrence of peripheral neuropathy. A neurotrophic ACTH(4-9) analogue, ORG 2766, is being studied for its protective effect. Possible modulatory effects of ORG 2766 on tumour cell growth and interference with the cytotoxic efficacy of VCR were studied in t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.90
更新日期：1994-03-01 00:00:00
abstract：BACKGROUND:Prescribing anti-programmed death-1 (PD-1) immunotherapy for advanced melanoma is currently not restricted by any biomarker assessment. Determination of programmed death-ligand-1 (PD-L1)-expression status is technically challenging and is not mandatory, because negative tumours also achieve therapeutic respo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-018-0168-9
更新日期：2018-07-01 00:00:00
