Abstract:
:Antibody drug conjugates (ADCs) employ the exquisite specificity of tumour-specific monoclonal antibodies (mAb) for the targeted delivery of highly potent cytotoxic drugs to the tumour site. The chemistry of the linker, which connects the drug to the mAb, determines how and when the drug is released from the mAb. This, as well as the chemistry of the drug, can dictate whether the drug can diffuse into surrounding cells, resulting in 'bystander killing'. Initially, any bystander killing mechanism of action of an ADC was understood to involve an essential sequence of steps beginning with surface antigen targeting, internalisation, intracellular linker cleavage, drug release, and diffusion of drug away from the targeted cell. However, recent studies indicate that, depending on the linker and drug combination, this mechanism may not be essential and ADCs can be cleaved extracellularly or via other mechanisms. In this minireview, we will examine the role of bystander killing by ADCs and explore the emerging evidence of how this can occur independently of internalisation.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Staudacher AH,Brown MPdoi
10.1038/bjc.2017.367subject
Has Abstractpub_date
2017-12-05 00:00:00pages
1736-1742issue
12eissn
0007-0920issn
1532-1827pii
bjc2017367journal_volume
117pub_type
杂志文章,评审abstract::To understand genetic events which play a role in the development and/or progression of human endometrial cancer, we studied allelotypes on all autosomal chromosomes, as well as chromosome X, with 42 microsatellite markers and 56 endometrial cancers. The most frequent loss of heterozygosity (LOH) was observed on the l...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.663
更新日期:1996-12-01 00:00:00
abstract::Phyto-oestrogens are plant compounds structurally similar to oestradiol, which have been proposed to have protective effects against breast cancer. The main class of phyto-oestrogens in the Western diet is lignans. Literature reports on the effect of lignans in breast cancer risk have been conflicting. We performed th...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/sj.bjc.6605003
更新日期:2009-05-05 00:00:00
abstract::Hyperthermia (42° C.) exerted an inhibitory effect on the O(2) uptake of rabbit VX2 carcinoma cells in vitro, and led to a decrease in viability and growth potential of the cells, as measured by their ability to produce tumours in rabbits. Anaerobic glycolysis of the tumour cells was unaltered by hyperthermia. Respira...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1971.91
更新日期:1971-12-01 00:00:00
abstract::Eighty-nine fresh tissue samples from flat colonic mucosa, polypoid lesions, macroscopically evident carcinomas, and metastatic carcinomas from ten patients with longstanding ulcerative colitis (greater than or equal to 8 years duration) were analysed by DNA flow cytometry and light microscopy. Of a total of ten carci...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.302
更新日期:1991-08-01 00:00:00
abstract:BACKGROUND:Overexpression of plasma membrane multi-drug resistance protein 1 (MRP-1) can lead to multidrug resistance. In this study, we describe for the first time the expression of mitochondrial MRP-1 in untreated human normal and cancer cells and tissues. METHODS:MRP-1 expression and subcellular localisation in nor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.40
更新日期:2012-03-13 00:00:00
abstract::This study addresses the hypothesis that altered expression of oestrogen receptor-beta and/or altered relative expression of coactivators and corepressors of oestrogen receptors are associated with and may be mechanisms of de novo tamoxifen resistance in oestrogen receptor positive breast cancer. All cases were oestro...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600654
更新日期:2002-12-02 00:00:00
abstract::Germline mutations in genes encoding proteins involved in DNA mismatch repair are responsible for the autosomal dominantly inherited cancer predisposition syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We describe here analysis of hMLH1 and hMSH2 in nine Greek families referred to our centre for HNPCC. A ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602260
更新日期:2005-01-31 00:00:00
abstract:BACKGROUND:Systemic inflammation measured by the neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and CRP/albumin ratio (CRP/Alb) was shown to impact the survival prognosis in patients with extracranial solid cancer. METHO...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01254-0
更新日期:2021-01-21 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::In addition to hypoxia, acidic extracellular pH (pH(e)) is recognised as one of the microenvironmental characteristics of solid tumours. A number of studies have examined ways to increase tumour acidity in order to improve tumour-specific targeting of certain drugs and the effectiveness of hyperthermia. However, previ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601766
更新日期:2004-05-04 00:00:00
abstract::Despite encouraging results from recent studies, there is still no consensus to undertake mass screening using the Haemoccult test in the general population. The success of mass screening for colorectal cancer depends among other things on Haemoccult test properties. In on-going screening programmes, the Haemoccult te...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.459
更新日期:1995-10-01 00:00:00
abstract:BACKGROUND:Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targete...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.120
更新日期:2013-04-30 00:00:00
abstract::The relationship between circulating C-reactive protein concentrations and potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8 (IL...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602248
更新日期:2004-12-13 00:00:00
abstract::Cellular senescence is an established tumour-suppressive mechanism that prevents the proliferation of premalignant cells. However, several lines of evidence show that senescent cells, which often persist in vivo, can also promote tumour progression in addition to other age-related pathologies via the senescence-associ...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.2016.115
更新日期:2016-05-24 00:00:00
abstract::No published data are available concerning the activity and tolerability of intramuscularly administered granulocyte colony-stimulating factor (G-CSF) in humans. To fill this gap, 19 patients with advanced ovarian cancer previously treated with at least one first-line chemotherapy cycle received the following myelosup...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1994.186
更新日期:1994-05-01 00:00:00
abstract::Four-coordinate (Pt(II)) platinum-based anticancer drugs are widely used in primary or palliative chemotherapy and produce considerable efficacy in certain clinical applications, for example testicular cancer. However, in many cancers the Pt(II) drugs are beset by poor efficacy mainly due to suboptimal pharmacokinetic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603854
更新日期:2007-07-16 00:00:00
abstract:BACKGROUND:To estimate the accuracy of one-step nucleic acid amplification (OSNA) assay as an intra-operative sentinel lymph node biopsy (SLNB) for sentinel lymph node (SLN) metastasis in breast cancer. METHODS:PubMed, Cochrane Library and Web of Science databases were searched by two independent reviewers to retrieve...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/bjc.2017.262
更新日期:2017-10-10 00:00:00
abstract::Regional chemotherapy is commonly used to treat patients with colorectal liver metastases. However, improvement in survival has still not been demonstrated. Cytotoxic loaded albumin microspheres for arterial administration have been described as a means of improving the the therapeutic index, but their distribution de...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.252
更新日期:1991-07-01 00:00:00
abstract::Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-spec...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605047
更新日期:2009-05-19 00:00:00
abstract::Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal-epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protea...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603006
更新日期:2006-04-24 00:00:00
abstract::The objective of this paper is to compare the hospital costs of treating patients with colorectal cancers detected as a result of a faecal occult blood screening programme with those of patients whose cancers present symptomatically (control group). Patient-specific cost estimates are made, using case records and hosp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.462
更新日期:1993-11-01 00:00:00
abstract:BACKGROUND:The arachidonic acid metabolite 12(S)-HETE is suspected to enhance metastatic spread by inducing cancer cell- and lymph endothelial cell (LEC) motility. However, the molecular mechanisms leading to 12(S)-HETE-triggered cell migration are still elusive. METHODS:To delineate the signalling pathways involved i...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.201
更新日期:2016-07-26 00:00:00
abstract:BACKGROUND:Panobinostat, a pan-deacetylase inhibitor, overcomes imatinib resistance in preclinical models of gastrointestinal stromal tumours (GIST). Here we determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of panobinostat in combination with imatinib (IM) for treatment of patients with re...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.826
更新日期:2014-03-04 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 toxicity of misonidazole (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) towards mammalian cells in vitro has been determined as a function of O2 tension. Misonidazole under hypoxic conditions (less than 10 Parts/10(6) O2) shows the greatest toxicity. Split-dose experiments indicate that lethal damage can be "repa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.172
更新日期:1978-07-01 00:00:00
abstract::Elderly patients are recommended to have a reduced starting dose (300 mg m(-2) once every 3 weeks) of irinotecan monotherapy. The aims of this analysis are to compare toxicity and survival according to age, performance status (PS), gender and prior radical pelvic radiotherapy (RT). The primary end points were overall ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.bjc.6602169
更新日期:2004-10-18 00:00:00
abstract::A retrospective case-control study of 200 patients with head and neck cancer, and 200 controls matched for age and sex, confirmed the importance of tobacco and alcohol consumption in the aetiology of malignant tumours of the upper gastrointestinal and upper respiratory tracts. A male-female ratio of 3:1 was found, and...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.26
更新日期:1981-02-01 00:00:00
abstract:BACKGROUND:Lymphovascular invasion (LVI) is associated with the development of metastasis in invasive breast cancer (BC). However, the complex molecular mechanisms of LVI, which overlap with other oncogenic pathways, remain unclear. This study, using available large transcriptomic datasets, aims to identify genes assoc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0486-6
更新日期:2019-06-01 00:00:00
abstract::The mature epidermal growth factor receptor (EGFR) neither associates with nor requires the molecular chaperone heat-shock protein 90 (Hsp90). Mutations in EGFR exons 18, 19, and 21 confer Hsp90 chaperone dependence. In non-small cell lung cancer (NSCLC), these mutations are associated with enhanced sensitivity to EGF...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603950
更新日期:2007-09-17 00:00:00
abstract::This is the first study to investigate the associations of IGF-1, IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer in prospectively collected blood samples from an Oriental population. Between 1986 and 1989 serum samples were collected at baseline from 18 244 men, aged 45-65 years, without a history...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2172
更新日期:2001-11-30 00:00:00