Abstract：
BACKGROUND:There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. METHODS:This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously develop after surgical resection of primary kidney or breast tumours derived from orthotopic implantation of murine cancer cell lines (RENCAluc or EMT-6/CDDP, respectively). RESULTS:In the RENCAluc model, adjuvant sunitinib plus anti-PD-L1 improved overall survival compared to either drug alone, while the same combination was ineffective as early therapy for unresected primary tumours or late-stage therapy for advanced metastatic disease. In the EMT-6/CDDP model, anti-PD-L1 was highly effective as an adjuvant monotherapy, while its combination with paclitaxel chemotherapy (with or without anti-VEGF) was most effective as a neoadjuvant therapy. CONCLUSIONS:Our preclinical data suggest that anti-PD-L1 plus sunitinib may warrant further investigation as an adjuvant therapy for RCC, while anti-PD-L1 may be improved by combining with chemotherapy in the neoadjuvant but not the adjuvant setting of treating breast cancer.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Wu FTH,Xu P,Chow A,Man S,Krüger J,Khan KA,Paez-Ribes M,Pham E,Kerbel RSdoi
10.1038/s41416-018-0297-1subject
Has Abstractpub_date
2019-01-01 00:00:00pages
196-206issue
2eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0297-1journal_volume
120pub_type
杂志文章abstract：BACKGROUND:Metastatic clear cell renal cell carcinoma (ccRCC) patients have <9% 5-year survival rate, do not respond well to targeted therapy and eventually develop resistance. A better understanding of molecular pathways of RCC metastasis is the basis for the discovery of novel prognostic markers and targeted therapie...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.828
更新日期：2014-03-04 00:00:00
abstract：:Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT(1)R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in ova...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602961
更新日期：2006-02-27 00:00:00
abstract：BACKGROUND:The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment ar...
journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/bjc.2014.504
更新日期：2014-11-25 00:00:00
abstract：BACKGROUND:Geriatric oncology guidelines state that fit older men with prostate cancer should receive curative treatment. In a population-based study, we investigated associations between age and non-receipt of curative treatment in men with localised prostate cancer, and the effect of clinical variables on this in dif...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.268
更新日期：2013-07-09 00:00:00
abstract：BACKGROUND:Topoisomerase I (Topo I) poisons (e.g., camptothecin (CPT)), used to treat cancer, cause DNA breaks that are most cytotoxic during S phase. PARP-1 promotes DNA repair and PARP inhibitors (PARPi) sensitise cells to Topo I poisons. We aimed to determine whether chemosensitisation is also S phase specific using...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.378
更新日期：2014-09-23 00:00:00
abstract：:In the first part of this study the availability of folinic acid (FA) and its main active circulating metabolite, 5-methyltetrahydrofolate (5-MTHF), were studied in plasma and cerebrospinal fluid (CSF) from normal subjects after i.v. administration of 100 and 250 mg of FA. 5-MTHF rapidly appeared in plasma, the maximu...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.127
更新日期：1989-04-01 00:00:00
abstract：:Epidermal growth factor receptor (EGFR) gene mutations and increased copy numbers are considered as predictors of response to EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC). Lung cancer diagnosis is often based on cytology alone. However, almost all published data on EGFR gene analyse...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604142
更新日期：2008-01-15 00:00:00
abstract：:The relation between pretreatment night-time urinary catecholamine excretion and chemotherapy-induced nausea and vomiting was studied. The first cohort included 17 women and three men with various cancer forms receiving low or moderately emetogenic chemotherapy. The second cohort included 42 women receiving cisplatinu...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/bjc.1994.364
更新日期：1994-10-01 00:00:00
abstract：:Differentiation-inducing ability of gamma-radiation, N,N-dimethylformamide and their combination has been tested on human rhabdomyosarcoma RMZ-RC2 clone cells. Ionising radiation at 2-5 Gy doses induced a more differentiated morphology, with the appearance of an increased proportion of multinuclear myotube-like cells,...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.107
更新日期：1992-04-01 00:00:00
abstract：:Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and a...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/s41416-020-01160-5
更新日期：2021-01-01 00:00:00
abstract：:Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factor...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602408
更新日期：2005-04-25 00:00:00
abstract：:Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This st...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.0918
更新日期：2000-01-01 00:00:00
abstract：:I.p. administration at several dose levels over periods of up to 12 weeks, or continuous i.v. infusion of high doses of misonidazole (MISO) for 15 h, produced no significant change in peripheral nerve conduction velocity (NCV) and did not prevent the normal increase in NCV as the animals matured from 12 to 24 weeks of...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1980.94
更新日期：1980-04-01 00:00:00
abstract：BACKGROUND:We analysed critically the potential usefulness of RNA- and DNA-based biomarkers in supporting conventional histological diagnostic tests for prostate carcinoma (PCa) detection. METHODS:Microarray profiling of gene expression and DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32 ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.337
更新日期：2014-08-12 00:00:00
abstract：BACKGROUND:This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:A total of 22 patient...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605917
更新日期：2010-10-26 00:00:00
abstract：BACKGROUND:Stathmin mediates cell migration and invasion in vitro, and metastasis in vivo. To investigate stathmin's role on the metastatic process, we performed integrated mRNA-miRNA expression analysis to identify pathways regulated by stathmin. METHODS:MiRNA and gene arrays followed by miRNA-target-gene integration...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0669-1
更新日期：2020-02-01 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：:Mismatch repair (MMR) deficiency in tumours from patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome is mainly caused by mutations in the MLH1, MSH2, and MSH6 genes. A major challenge in the clinical management of patients with suspected HNPCC is the frequent occurrence of missense mutations i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602129
更新日期：2004-10-04 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：BACKGROUND:Antihypertensives may inhibit pancreatic carcinogenesis. We examined the association between use of these drugs and pancreatic cancer in patients with chronic pancreatitis. METHODS:We conducted a nationwide population-based cohort study of all chronic pancreatitis patients diagnosed in Denmark during 1996-2...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0562-y
更新日期：2019-10-01 00:00:00
abstract：:The expression of urokinase-type plasminogen activator (uPA) was investigated in squamous cell carcinoma of the human larynx. For this purpose, tissue extracts from 25 matched samples of normal mucosa and neoplastic larynx were compared for the levels of uPA activity as evaluated by a chromogenic PA assay and sodium d...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.512
更新日期：1996-10-01 00:00:00
abstract：:In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk (estimate 1.31, 95% CI 1.1-1.6), providing indirect support for the hypothesis that in utero hormone variations influence risk of testicular cancer. The summary-estimate for dizygotic twins was 1.3 (1.0-1.7) and for monozygotic or same se...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析
doi：10.1038/sj.bjc.6604136
更新日期：2008-01-15 00:00:00
abstract：:To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months w...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.93
更新日期：1993-03-01 00:00:00
abstract：:Cell fusion has been used to analyse the genetic determinants of metastasis at the cellular level. Highly metastatic mouse melanoma cells were fused with diploid mouse lymphocytes and a range of hybrid clones isolated and tested for tumorigenicity and metastatic potential by s.c. injection into newborn, histocompatibl...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1983.60
更新日期：1983-03-01 00:00:00
abstract：:The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 "functional" binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its par...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600067
更新日期：2002-02-01 00:00:00
abstract：:Nabilone, a synthetic cannabinoid, and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide, Adriamycin and Etoposide. Symptom scores were significantly better for patients on nabilone for nausea, retching and...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1983.247
更新日期：1983-11-01 00:00:00
abstract：BACKGROUND:The recognition that cancer is not a single entity, rather that different cancers have different causes and trajectories, has been a key development in the scientific understanding of cancer. However, little is known about the British public's awareness of differences between cancers. This study examined dif...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.185
更新日期：2012-06-05 00:00:00
abstract：:The limited prognosis of patients with castration-resistant prostate cancer (CRPC) on existing hormonal manipulation therapies calls out for the urgent need for new management strategies. The novel, orally available, small-molecule compound, abiraterone acetate, is undergoing evaluation in early clinical trials and em...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6604904
更新日期：2009-03-10 00:00:00
abstract：:To examine whether weight loss at presentation influences outcome in patients who received chemotherapy for lung cancer or mesothelioma. Multivariate analysis of prospectively collected data 1994-2001. Data were available for age, gender, performance status, histology, stage, response, toxicity, progression-free and o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601781
更新日期：2004-05-17 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
