Abstract：
:Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour architecture. This is a particular problem for the preclinical testing of immunotherapies, as these agents require an intact tumour human-specific microenvironment for them to be effective. In this review, we explore the potential of patient-derived explants (PDEs) for fulfilling this need. PDEs involve the ex vivo culture of fragments of freshly resected human tumours that retain the histological features of original tumours. PDE methodology for anti-cancer drug testing has been in existence for many years, but the platform has not been widely adopted in translational research facilities, despite strong evidence for its clinical predictivity. By modifying PDE endpoint analysis to include the spatial profiling of key biomarkers by using multispectral imaging, we argue that PDEs offer many advantages, including the ability to correlate drug responses with tumour pathology, tumour heterogeneity and changes in the tumour microenvironment. As such, PDEs are a powerful model of choice for cancer drug and biomarker discovery programmes.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Powley IR,Patel M,Miles G,Pringle H,Howells L,Thomas A,Kettleborough C,Bryans J,Hammonds T,MacFarlane M,Pritchard Cdoi
10.1038/s41416-019-0672-6subject
Has Abstractpub_date
2020-03-01 00:00:00pages
735-744issue
6eissn
0007-0920issn
1532-1827pii
10.1038/s41416-019-0672-6journal_volume
122pub_type
杂志文章,评审abstract：:Common warts could indicate cervical cancer susceptibility, as both are caused by human papillomavirus (HPV). Eczema was also investigated, as atopic eczema has been negatively associated with warts, but non-atopic eczema may be associated with compromised host defences, as observed in patients with HIV, suggesting in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600585
更新日期：2002-10-21 00:00:00
abstract：BACKGROUND:Cross-talk between receptor tyrosine kinases and the oestrogen receptor (ER) is implicated in resistance to endocrine therapy. We investigated whether AEE788 (a combined inhibitor of EGFR, HER2 and VEGFR) plus tamoxifen or letrozole enhanced the individual anti-tumour effects of these agents. METHODS:Breast...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605641
更新日期：2010-04-13 00:00:00
abstract：:The cytotoxicity of three platinum complexes, cis-diamminedichloroplatinum(II) (cis-platin), cis-dichloro-trans-dihydroxy-cis-bis (isopropylamine) platinum(IV), (CHIP) and diammine (1, 1-cyclobutane-dicarboxylato) platinum(II) (carboplatin) on Chinese Hamster ovary (CHO) and mouse sarcoma RIF-1 cells cultured in vitro...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.126
更新日期：1988-06-01 00:00:00
abstract：:This study provides an analysis of the structure of the initial cancer consultation, the consultation styles of medical and radiation oncologists, and their effect on patient outcomes. One hundred and fifty-five cancer patients attending their first consultation with either a medical or radiation oncologist were audio...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604348
更新日期：2008-05-06 00:00:00
abstract：:Development of thermotolerance is an important phenomenon that must be considered when thermochemotherapy with multiple heat treatments is used clinically. To study the effect of thermotolerance on cellular cisplatin (cDDP) sensitivity at 37 degrees C and 43 degrees C in cell lines with different cDDP sensitivities, t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.100
更新日期：1995-03-01 00:00:00
abstract：:All hospital-treated cases of Burkitt's lymphoma (BL), with onset of symptoms in the period 1963-68 and resident in the Lango and Acholi districts of Uganda, were identified. The average annual incidence of BL in the 6-year period was 1-87 X 10(-5), similar to that in the adjacent West Nile district. Contrary to findi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.102
更新日期：1977-05-01 00:00:00
abstract：:Fifty patients affected by histologically confirmed gastrointestinal tract cancer (GTC) were treated with oral tegafur (TG) 1,000 mg m-2 p.o. on days 1-14 repeated after a 14 day interval. Out of 42 evaluable patients seven patients had a partial response (PR. 17%) with a median duration of 20.5 weeks, three had a min...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.105
更新日期：1990-03-01 00:00:00
abstract：:The aim of this study was to determine the dose-limiting toxicity (DLT) and establish the recommended dose for mitomycin C added every 3 weeks to the standard combination dose of capecitabine. Cohorts of at least three patients with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2) orally twice...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/sj.bjc.6602025
更新日期：2004-08-31 00:00:00
abstract：BACKGROUND:Our previous study demonstrated that extracellular adenosine 5'-triphosphate (ATP) stimulated prostate cancer cell invasion via P2Y receptors. However, the purinergic receptor subtype(s) involved in this process remains unclear. Here we aimed to determine whether P2Y2, one subtype of P2Y receptors, was invol...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.484
更新日期：2013-09-17 00:00:00
abstract：:Maturation of monocytes into macrophages in vitro has been assayed by a quantitative microtitre assay in patients with squamous-cell carcinoma of the lung. Monocyte maturation in autologous serum was significantly depressed in patients with both limited and extensive disease compared with normal controls, patients wit...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.71
更新日期：1981-04-01 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：:Chromosome 9p21 gene copy number in Ewing's sarcoma family of tumour (ESFT) cell lines and primary ESFT has been evaluated using Multiplex Ligation-dependent probe amplification, and the clinical significance of CDKN2A loss and p16/p14(ARF) expression investigated. Homozygous deletion of CDKN2A was identified in 4/9 (...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603819
更新日期：2007-06-18 00:00:00
abstract：:To investigate the usefulness of thyroglobulin mRNA (Tg-mRNA) detection in peripheral blood in the follow-up of papillary and follicular (differentiated) thyroid cancer, a literature study was performed. Both evidence for and evidence against the usefulness of Tg-mRNA detection were found. Also, evidence for the expre...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6601991
更新日期：2004-07-19 00:00:00
abstract：:A representative sample of 4657 adults greater than or equal to 45 years of age from the 5 main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos and Hawaiians) were interviewed during 1977-1979 regarding their diets. Quantitative food-consumption histories were obtained, from which average daily intak...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.189
更新日期：1981-09-01 00:00:00
abstract：:Pancreatic tumours are scirrhous, avascular tumours, suggesting that they may produce angiogenesis inhibitors that suppress the growth of the vasculature to the tumour and metastases. We have sought evidence for the angiogenesis inhibitor, endostatin, in normal and cancerous pancreatic tissue. Using Western blotting, ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602234
更新日期：2005-01-17 00:00:00
abstract：BACKGROUND:Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on ce...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.294
更新日期：2011-09-06 00:00:00
abstract：:The role of secreted frizzled-related protein (SFRP) genes in gastric cancer remains largely unknown. We determined the frequency and functional significance of SFRPs hypermethylation in human gastric cancer. The expression and methylation status of four SFRP members (SFRP1, 2, 4, and 5) in primary gastric cancer samp...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603968
更新日期：2007-10-08 00:00:00
abstract：:Decreased accumulation of the fluorescent dye BCECF [2', 7'-bis-(2-carboxyethyl)-5-(6)- carboxyfluorescein] characterized murine and human multidrug-resistant cell lines overexpressing the multidrug resistance protein (MRP). Indomethacin (10 microM), a known cyclo-oxygenase and glutathione-S-transferase inhibitor as w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.145
更新日期：1997-01-01 00:00:00
abstract：:To assess tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of the dual epidermal growth factor receptor (EGFR) 1 and 2 (HER2) tyrosine kinase inhibitor BIBW 2992. An escalating schedule of once-daily (OD) BIBW 2992 for 14 days followed by 14 days off medication was explored. Thirty-eigh...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604108
更新日期：2008-01-15 00:00:00
abstract：BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) patients frequently develop treatment resistance to cetuximab, a monoclonal antibody against EGFR, as well as radiotherapy. Here we addressed extracellular signal-regulated kinase 1/2 (ERK1/2) regulation by cetuximab or fractionated irradiation (IR) and conducted...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0892-9
更新日期：2020-07-01 00:00:00
abstract：BACKGROUND:Colorectal cancer (CRC) diagnoses and disease-specific survival (DSS) vary between ethnic groups in the United States. However, few studies have assessed differences among Asian subgroups. METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with invasive CRC...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.97
更新日期：2013-04-16 00:00:00
abstract：:The idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical work has now demonstrated that in addition to direct cytotoxic effects on cancer cells, a proportion...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/bjc.2017.376
更新日期：2018-02-06 00:00:00
abstract：:The death certificate only (DCO) index, which quantifies the proportion of patients for whom the death certificate provides the only notification to the registry, is a widely used measure of incompleteness of population-based cancer registration. This paper provides an algebraic assessment and a quantitative illustrat...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.363
更新日期：1995-08-01 00:00:00
abstract：:Cytochrome P450 3A is a drug-metabolising enzyme activity due to CYP3A4 and CYP3A5 gene products, that is involved in the inactivation of anticancer drugs. This study analyses the potential of cytochrome P450 3A enzyme in human colorectal cancer to impact anticancer therapy with drugs that are cytochrome P450 3A subst...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600494
更新日期：2002-09-09 00:00:00
abstract：:Accuracy in the assessment of performance status by oncologists has not been well evaluated. We investigated possible discrepancies in the assessment of performance status among patients, nurses, and oncologists, and evaluated the prognostic importance of each assessment. Two hundred and six inpatients with inoperable...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.2162
更新日期：2001-11-30 00:00:00
abstract：:Many theories mention hypersensitive, promiscuous, outlaw or bypass signalling pathways to explain the acquisition of hormone independence in prostate cancer. Hormonal escape of prostate tumours is marked by many biological changes, including mucinous and neuroendocrine differentiation. Since expression of several muc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601570
更新日期：2004-02-09 00:00:00
abstract：:To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg(-1)), receiving ATN-161 administered as a 10-min infusion th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603171
更新日期：2006-06-05 00:00:00
abstract：BACKGROUND:Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.56
更新日期：2013-03-19 00:00:00
abstract：BACKGROUND:Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast can...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.44
更新日期：2011-03-15 00:00:00
abstract：:In a case-control study, we investigated 169 women aged 15-49 years with malignant melanoma notified to the Oxford and South Western cancer registries during the years 1971-1976, together with 507 matched controls. Data about medical, reproductive, drug and smoking histories were obtained both by reviewing general pra...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.145
更新日期：1981-07-01 00:00:00
