Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease.


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.


Br J Cancer


Wu FTH,Xu P,Chow A,Man S,Krüger J,Khan KA,Paez-Ribes M,Pham E,Kerbel RS




Has Abstract


2019-01-01 00:00:00














  • Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk.

    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


    authors: Zheng T,Holford TR,Zahm SH,Owens PH,Boyle P,Zhang Y,Zhang B,Wise JP Sr,Stephenson LP,Ali-Osman F

    更新日期:2003-01-13 00:00:00

  • How to evaluate the risk/benefit of trimodality therapy in locally advanced non-small-cell lung cancer.

    abstract::The trimodality approach represented by concurrent chemoradiotherapy followed by surgical resection is a highly effective, but potentially toxic therapy for locally advanced non-small-cell lung cancer (NSCLC). In this review, we discuss the current status of this therapy in patients with mediastinal node-positive (N2)...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审


    authors: Kunitoh H,Suzuki K

    更新日期:2007-05-21 00:00:00

  • Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma.

    abstract::This phase II study was designed to evaluate the activity and safety of a combination of irinotecan, docetaxel and oxaliplatin in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Forty patients with measurable distant metastasis received irinotecan 150 mg m(-2) and docetaxel 60 mg m(-2) on day 1, ...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Di Lauro L,Nunziata C,Arena MG,Foggi P,Sperduti I,Lopez M

    更新日期:2007-09-03 00:00:00

  • Syndecan-1 expression has prognostic significance in head and neck carcinoma.

    abstract::The syndecans are a family of cell-surface heparan sulphate proteoglycans that regulate cell behaviour by binding extracellular matrix molecules such as growth factors. The syndecan family has four members, of which syndecan-1 is the most studied and best characterized. We have studied the prognostic significance of s...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Anttonen A,Kajanti M,Heikkilä P,Jalkanen M,Joensuu H

    更新日期:1999-02-01 00:00:00

  • SupraMolecular BioVectors (SMBV) improve antisense inhibition of erbB-2 expression.

    abstract::New therapeutic strategies are now being developed against adenocarcinoma associated with erbB-2 amplification, particularly by inhibiting p185erbB-2 expression. Antisense oligodeoxynucleotides seem promising for this purpose as long as they are efficiently protected against degradation and targeted into the cells. We...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Allal C,Sixou S,Kravtzoff R,Soulet N,Soula G,Favre G

    更新日期:1998-05-01 00:00:00

  • Binding of TGF-beta1 latency-associated peptide (LAP) to alpha(v)beta6 integrin modulates behaviour of squamous carcinoma cells.

    abstract::The integrin alpha(v)beta6 is not detectable on normal keratinocytes in vivo but expression is increased significantly in oral squamous cell carcinoma where this heterodimer has been shown to play a role in cell migration, invasion and protease expression. Although regarded initially as a fibronectin receptor, alpha(v...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Thomas GJ,Hart IR,Speight PM,Marshall JF

    更新日期:2002-10-07 00:00:00

  • Differential expression of translation-associated genes in benign and malignant human breast tumours.

    abstract::The human gene sequences encoding the translation-associated functions of alpha-subunit of elongation factor 1 (EF-1 alpha) and the ubiquitin carboxyl extension protein (HUBCEP80) have been isolated by differential cDNA screening, and found to have significantly higher levels of expression in fibroadenomas (benign) co...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Adams SM,Sharp MG,Walker RA,Brammar WJ,Varley JM

    更新日期:1992-01-01 00:00:00

  • Association of medullary carcinoma of the thyroid with carcinoembryonic antigen.

    abstract::To investigate the association between medullary carcinoma of the thyroid (MCT) and carcinoembryonic antigen (CEA), we assayed 78 sera from patients with thyroid diseases for CEA, employing the radioimmunoassay of double antibody technique. All 13 sera from patients with MCT had high levels of CEA, ranging from 14 to ...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Ishikawa N,Hamada S

    更新日期:1976-08-01 00:00:00

  • The systemic inflammatory response, performance status and survival in patients undergoing alpha-interferon treatment for advanced renal cancer.

    abstract::The prognostic value of C-reactive protein, compared with ECOG performance status (ECOG-ps), in patients receiving alpha-interferon treatment for advanced renal cancer was assessed in 58 patients. In all, 55 patients died on follow-up. On multivariate analysis with ECOG-ps and C-reactive protein entered as covariates,...

    journal_title:British journal of cancer

    pub_type: 临床试验,杂志文章


    authors: Bromwich E,McMillan DC,Lamb GW,Vasey PA,Aitchison M

    更新日期:2004-10-04 00:00:00

  • Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma.

    abstract:BACKGROUND:HOX transcript antisense RNA (HOTAIR), which is expressed from the homebox C gene (HOXC) locus, is capable of reprogramming chromatin organisation and promoting cancer cell metastasis and can simultaneously bind the polycomb repressive complex 2, which enhances H3K27 trimethylation, and the LSD1-CoREST-REST ...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Li X,Wu Z,Mei Q,Li X,Guo M,Fu X,Han W

    更新日期:2013-10-15 00:00:00

  • Duck hepatitis B virus infection, aflatoxin B1 and liver cancer in domestic Chinese ducks.

    abstract::The oncogenicity of Duck hepatitis B virus (DHBV) is unclear since hepatocellular carcinomas (HCCs) have been reported only in domestic ducks in Qidong, an area of China where hepatitis B virus (HBV) and aflatoxin B1 (AFB1) are risk factors for liver cancer in man. In order to better define the association between DHB...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Cova L,Mehrotra R,Wild CP,Chutimataewin S,Cao SF,Duflot A,Prave M,Yu SZ,Montesano R,Trepo C

    更新日期:1994-01-01 00:00:00

  • HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.

    abstract:BACKGROUND:In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in t...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Martin V,Landi L,Molinari F,Fountzilas G,Geva R,Riva A,Saletti P,De Dosso S,Spitale A,Tejpar S,Kalogeras KT,Mazzucchelli L,Frattini M,Cappuzzo F

    更新日期:2013-02-19 00:00:00

  • Enhancement of transforming growth factor-alpha synthesis in multicellular tumour spheroids of A431 squamous carcinoma cells.

    abstract::Multicellular tumour spheroids are cellular aggregates that can be prepared from many types of tumour cells. These three-dimensional structures provide a model for analysing the effects of cell-cell contact and intercellular microenvironments on phenomena such as autocrine regulation of growth factor synthesis. Autore...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Laderoute KR,Murphy BJ,Short SM,Grant TD,Knapp AM,Sutherland RM

    更新日期:1992-02-01 00:00:00

  • Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin.

    abstract::We have investigated the production, growth and inactivation of gastrin-releasing peptide (GRP)-like peptides in human breast cancer cell lines. Radioimmunoassay detected GRP-like immunoreactivity (GRP-LI) in T47D breast cancer cells but not in the conditioned medium, indicating rapid clearance. No GRP-LI was found in...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Burns DM,Walker B,Gray J,Nelson J

    更新日期:1999-01-01 00:00:00

  • Expression of topoisomerase II alpha and beta in an adenocarcinoma cell line carrying amplified topoisomerase II alpha and retinoic acid receptor alpha genes.

    abstract::Human topoisomerase II enzymes are targets for a number of widely used anticancer agents. We have analysed a lung adenocarcinoma cell line CALU3, which has co-amplified topoisomerase II alpha and ERBB2 sequences, for the structure of the amplicon and for expression of both topoisomerase II alpha and beta. The region o...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Coutts J,Plumb JA,Brown R,Keith WN

    更新日期:1993-10-01 00:00:00

  • Modulation of endogenous beta-tubulin isotype expression as a result of human beta(III)cDNA transfection into prostate carcinoma cells.

    abstract::Increases of individual beta tubulin isotypes in antimicrotubule drug resistant cell lines have been reported by several laboratories. We have previously described elevations in beta(III)and beta(IVa)isotypes in estramustine and paclitaxel resistant human prostate carcinoma cells. To investigate further the function o...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Ranganathan S,McCauley RA,Dexter DW,Hudes GR

    更新日期:2001-09-01 00:00:00

  • Immunotoxicity of multiple dosing regimens of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.

    abstract::We have shown that doxorubicin entrapped in cardiolipin liposomes retain antitumour efficacy in mice but had diminished cardiac uptake and cardiotoxicity. Such liposomes are preferentially taken up by spleen. In a previous study we showed that a single dose of liposomal doxorubicin is not more toxic than free doxorubi...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Rahman A,Joher A,Neefe JR

    更新日期:1986-09-01 00:00:00

  • Flow cytometric analysis of cell surface carbohydrates in metastatic human breast cancer.

    abstract::Helix pomatia agglutinin (HPA)- and Concanavalin A (Con A)-binding carbohydrate expression were studied on 32 tumour samples from primary adenocarcinoma of the breast and 12 samples from lymph node metastases. Live cells were spilled from each of the fresh samples and the extent of fluorescent-labelled HPA and Con A-b...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Alam SM,Whitford P,Cushley W,George WD,Campbell AM

    更新日期:1990-08-01 00:00:00

  • A controlled "before-after" study: impact of a clinical guidelines programme and regional cancer network organization on medical practice.

    abstract::A regional cancer network has been set up in the Rhône-Alpes region in France. The aim of the project is to improve the quality of care and to rationalize prescriptions in the network. In this network, we assessed the impact of the implementation of a clinical practice guidelines project by assessing the conformity of...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Ray-Coquard I,Philip T,de Laroche G,Froger X,Suchaud JP,Voloch A,Mathieu-Daudé H,Fervers B,Farsi F,Browman GP,Chauvin F

    更新日期:2002-02-01 00:00:00

  • Definition of the role of chromosome 9p21 in sporadic melanoma through genetic analysis of primary tumours and their metastases. The Melanoma Cooperative Group.

    abstract::Malignant melanoma (MM) is thought to arise by sequential accumulation of genetic alterations in normal melanocytes. Previous cytogenetic and molecular studies indicated the 9p21 as the chromosomal region involved in MM pathogenesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19(ARF), frequently inacti...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Palmieri G,Cossu A,Ascierto PA,Botti G,Strazzullo M,Lissia A,Colombino M,Casula M,Floris C,Tanda F,Pirastu M,Castello G,Melanoma Cooperative Group.

    更新日期:2000-12-01 00:00:00

  • Comparison of survival between malignant neuroendocrine tumours of midgut and pancreatic origin.

    abstract::The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognos...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Johanson V,Tisell LE,Olbe L,Wängberg B,Nilsson O,Ahlman H

    更新日期:1999-06-01 00:00:00

  • Cancer-associated fibroblasts-heroes or villains?

    abstract::Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, mor...

    journal_title:British journal of cancer

    pub_type: 杂志文章,评审


    authors: Gieniec KA,Butler LM,Worthley DL,Woods SL

    更新日期:2019-08-01 00:00:00

  • Risk of lung cancer associated with residential radon exposure in south-west England: a case-control study.

    abstract::Studies of underground miners occupationally exposed to radon have consistently demonstrated an increased risk of lung cancer in both smokers and non-smokers. Radon exposure also occurs elsewhere, especially in houses, and estimates based on the findings for miners suggest that residential radon is responsible for abo...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Darby S,Whitley E,Silcocks P,Thakrar B,Green M,Lomas P,Miles J,Reeves G,Fearn T,Doll R

    更新日期:1998-08-01 00:00:00

  • Birth characteristics and risk of Wilms' tumour: a nationwide prospective study in Norway.

    abstract::Relationships between incidence of Wilms' tumour and information recorded at birth were investigated in a prospective study of the 1,489,297 children born in Norway between 1967 and 1992. A total of 119 individuals were diagnosed with Wilms' tumour in the age interval 0-14 years. A high length at birth was significant...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Heuch JM,Heuch I,Kvåle G

    更新日期:1996-10-01 00:00:00

  • Adriamycin/cyclophosphamide and adriamycin/melphalan in advanced L1210 leukaemia.

    abstract::Adriamycin and cyclophosphamide are active agents in human and experimental tumours. Using the L1210 murine leukaemia, their effectiveness alone and in combination was studied. The combination is highly synergistic in this tumour, resulting in a greater than 50% survival rate when the agents used alone at optimal dose...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Tobias JS,Parker LM,Tattersall MH,Frei E 3rd

    更新日期:1975-08-01 00:00:00

  • VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma.

    abstract::Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and spec...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Beckermann BM,Kallifatidis G,Groth A,Frommhold D,Apel A,Mattern J,Salnikov AV,Moldenhauer G,Wagner W,Diehlmann A,Saffrich R,Schubert M,Ho AD,Giese N,Büchler MW,Friess H,Büchler P,Herr I

    更新日期:2008-08-19 00:00:00

  • Cytotoxic drugs efficacy correlates with adipose tissue docosahexaenoic acid level in locally advanced breast carcinoma.

    abstract::Experimental studies indicated that long-chain polyunsaturated fatty acids may increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate this hypothesis in breast cancer, we have prospectively studied the association between levels of fatty acids stored in breast adipose tissue and the response o...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Bougnoux P,Germain E,Chajès V,Hubert B,Lhuillery C,Le Floch O,Body G,Calais G

    更新日期:1999-04-01 00:00:00

  • DNA methylation analysis in self-sampled brush material as a triage test in hrHPV-positive women.

    abstract:BACKGROUND:Primary high-risk human papillomavirus (hrHPV) testing in cervical cancer screening shows relatively low specificity, which makes triage testing necessary. In this study, DNA methylation analysis was compared with cytology for triage testing in hrHPV-positive women. Moreover, feasibility of DNA methylation a...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Boers A,Bosgraaf RP,van Leeuwen RW,Schuuring E,Heideman DA,Massuger LF,Verhoef VM,Bulten J,Melchers WJ,van der Zee AG,Bekkers RL,Wisman GB

    更新日期:2014-09-09 00:00:00

  • Erythrocyte sedimentation rate and anaemia are independent predictors of survival in patients with clear cell renal cell carcinoma.

    abstract:BACKGROUND:The 1997 international consensus conference on renal cell cancer (RCC) prognosis suggested erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and anaemia as prognostic biomarkers, but most studies reviewed were limited by small sample sizes. METHODS:The Cox proportional hazards model was used...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Choi Y,Park B,Kim K,Jeong BC,Seo SI,Jeon SS,Choi HY,Lee JE,Lee HM

    更新日期:2013-02-05 00:00:00

  • Binding of misonidazole to hypoxic cells in monolayer and spheroid culture: evidence that a side-chain label is bound as efficiently as a ring label.

    abstract::The binding of ring-labelled and side-chain labelled misonidazole to hypoxic cells in monolayer and spheroid cultures of mammalian cells has been compared. The kinetics and patterns of binding for the two labelled compounds are indistinguishable. This finding has implications for the mechanism of binding and for the d...

    journal_title:British journal of cancer

    pub_type: 杂志文章


    authors: Raleigh JA,Franko AJ,Koch CJ,Born JL

    更新日期:1985-02-01 00:00:00