Postsurgical adjuvant tumor therapy by combining anti-angiopoietin-2 and metronomic chemotherapy limits metastatic growth.


:Antiangiogenic tumor therapy has failed in the adjuvant setting. Here we show that inhibition of the Tie2 ligand angiopoietin-2 (Ang2) effectively blocks metastatic growth in preclinical mouse models of postsurgical adjuvant therapy. Ang2 antibody treatment combines well with low-dose metronomic chemotherapy (LDMC) in settings in which maximum-dose chemotherapy does not prove effective. Mechanistically, Ang2 blockade could be linked to quenching the inflammatory and angiogenic response of endothelial cells (ECs) in the metastatic niche. Reduced EC adhesion molecule and chemokine expression inhibits the recruitment of tumor-promoting CCR2(+)Tie2(-) metastasis-associated macrophages. Moreover, LDMC contributes to therapeutic efficacy by inhibiting the recruitment of protumorigenic bone marrow-derived myeloid cells. Collectively, these data provide a rationale for mechanism-guided adjuvant tumor therapies.


Cancer Cell


Cancer cell


Srivastava K,Hu J,Korn C,Savant S,Teichert M,Kapel SS,Jugold M,Besemfelder E,Thomas M,Pasparakis M,Augustin HG




Has Abstract


2014-12-08 00:00:00














  • Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells.

    abstract::T cell engineering is a powerful means to rapidly generate anti-tumor T cells. The costimulatory properties of second-generation chimeric antigen receptors (CARs) determine the overall potency of adoptively transferred T cells. Using an in vivo "stress test" to challenge CD19-targeted T cells, we studied the functiona...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Zhao Z,Condomines M,van der Stegen SJC,Perna F,Kloss CC,Gunset G,Plotkin J,Sadelain M

    更新日期:2015-10-12 00:00:00

  • In Search of a Cure for Proteostasis-Addicted Cancer: A AAA Target Revealed.

    abstract::Tumorigenesis is often associated with an unbalanced protein homeostasis (proteostasis) network, which sensitizes cancer cells to drugs targeting protein quality control (PQC) regulators. In this issue of Cancer Cell, Anderson and colleagues investigated the anti-cancer activity of a new class of inhibitor against a m...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Xia D,Ye Y

    更新日期:2015-11-09 00:00:00

  • A tell-tail sign of chromatin: histone mutations drive pediatric glioblastoma.

    abstract::Recent genomic analyses of pediatric glioblastoma, a poorly understood tumor with dismal outcome, have identified mutations in histone H3 variants that affect critical amino acids in the tail. The findings extend discoveries of chromatin regulator inactivation and gain-of-function mutations by documenting alteration o...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Rheinbay E,Louis DN,Bernstein BE,Suvà ML

    更新日期:2012-03-20 00:00:00

  • Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy.

    abstract::We demonstrate that concurrent administration of poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors is effective in inhibiting tumor growth but poorly tolerated. Concurrent treatment with PARP and WEE1 inhibitors induces replication stress, DNA damage, and abrogates the G2 DNA damage checkpoint in both normal and ...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Fang Y,McGrail DJ,Sun C,Labrie M,Chen X,Zhang D,Ju Z,Vellano CP,Lu Y,Li Y,Jeong KJ,Ding Z,Liang J,Wang SW,Dai H,Lee S,Sahni N,Mercado-Uribe I,Kim TB,Chen K,Lin SY,Peng G,Westin SN,Liu J,O'Connor MJ,Yap T

    更新日期:2019-06-10 00:00:00

  • Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity.

    abstract::We characterized the landscape and drug sensitivity of ERBB2 (HER2) mutations in cancers. In 11 datasets (n = 211,726), ERBB2 mutational hotspots varied across 25 tumor types. Common HER2 mutants yielded differential sensitivities to eleven EGFR/HER2 tyrosine kinase inhibitors (TKIs) in vitro, and molecular dynamics s...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Robichaux JP,Elamin YY,Vijayan RSK,Nilsson MB,Hu L,He J,Zhang F,Pisegna M,Poteete A,Sun H,Li S,Chen T,Han H,Negrao MV,Ahnert JR,Diao L,Wang J,Le X,Meric-Bernstam F,Routbort M,Roeck B,Yang Z,Raymond VM,Lanman

    更新日期:2019-10-14 00:00:00

  • A Platform of Synthetic Lethal Gene Interaction Networks Reveals that the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway through FAK.

    abstract::Activating mutations in GNAQ/GNA11, encoding Gαq G proteins, are initiating oncogenic events in uveal melanoma (UM). However, there are no effective therapies for UM. Using an integrated bioinformatics pipeline, we found that PTK2, encoding focal adhesion kinase (FAK), represents a candidate synthetic lethal gene with...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Feng X,Arang N,Rigiracciolo DC,Lee JS,Yeerna H,Wang Z,Lubrano S,Kishore A,Pachter JA,König GM,Maggiolini M,Kostenis E,Schlaepfer DD,Tamayo P,Chen Q,Ruppin E,Gutkind JS

    更新日期:2019-03-18 00:00:00

  • Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner.

    abstract::TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic d...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Mancini A,Xavier-Magalhães A,Woods WS,Nguyen KT,Amen AM,Hayes JL,Fellmann C,Gapinske M,McKinney AM,Hong C,Jones LE,Walsh KM,Bell RJA,Doudna JA,Costa BM,Song JS,Perez-Pinera P,Costello JF

    更新日期:2018-09-10 00:00:00

  • Clinically Actionable Strategies for Studying Neural Influences in Cancer.

    abstract::Neuro-glial activation is a recently identified hallmark of growing cancers. Targeting tumor hyperinnervation in preclinical and small clinical trials has yielded promising antitumor effects, highlighting the need of systematic analysis of neural influences in cancer (NIC). Here, we outline the strategies translating ...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Demir IE,Reyes CM,Alrawashdeh W,Ceyhan GO,Deborde S,Friess H,Görgülü K,Istvanffy R,Jungwirth D,Kuner R,Maryanovich M,Na'ara S,Renders S,Saloman JL,Scheff NN,Steenfadt H,Stupakov P,Thiel V,Verma D,Yilmaz BS,White R

    更新日期:2020-07-13 00:00:00

  • Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.

    abstract::The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Hayakawa Y,Ariyama H,Stancikova J,Sakitani K,Asfaha S,Renz BW,Dubeykovskaya ZA,Shibata W,Wang H,Westphalen CB,Chen X,Takemoto Y,Kim W,Khurana SS,Tailor Y,Nagar K,Tomita H,Hara A,Sepulveda AR,Setlik W,Gershon MD,

    更新日期:2015-12-14 00:00:00

  • An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.

    abstract::To define the mutation spectrum in non-Down syndrome acute megakaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL samples. Our analysis ident...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Gruber TA,Larson Gedman A,Zhang J,Koss CS,Marada S,Ta HQ,Chen SC,Su X,Ogden SK,Dang J,Wu G,Gupta V,Andersson AK,Pounds S,Shi L,Easton J,Barbato MI,Mulder HL,Manne J,Wang J,Rusch M,Ranade S,Ganti R,Parker M,

    更新日期:2012-11-13 00:00:00

  • Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF.

    abstract::Activating mutations in BRAF are the most common genetic alterations in melanoma. Inhibition of BRAF by small molecules leads to cell-cycle arrest and apoptosis. We show here that BRAF inhibition also induces an oxidative phosphorylation gene program, mitochondrial biogenesis, and the increased expression of the mitoc...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Haq R,Shoag J,Andreu-Perez P,Yokoyama S,Edelman H,Rowe GC,Frederick DT,Hurley AD,Nellore A,Kung AL,Wargo JA,Song JS,Fisher DE,Arany Z,Widlund HR

    更新日期:2013-03-18 00:00:00

  • The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function.

    abstract::Tumors constitute highly suppressive microenvironments in which infiltrating T cells are "exhausted" by inhibitory receptors such as PD-1. Here we identify TIGIT as a coinhibitory receptor that critically limits antitumor and other CD8(+) T cell-dependent chronic immune responses. TIGIT is highly expressed on human an...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Johnston RJ,Comps-Agrar L,Hackney J,Yu X,Huseni M,Yang Y,Park S,Javinal V,Chiu H,Irving B,Eaton DL,Grogan JL

    更新日期:2014-12-08 00:00:00

  • Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease.

    abstract::Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) initiated by expression of the p210-BCR-ABL fusion protein. We demonstrate in a murine model of p210-BCR-ABL-induced MPD that gene targeting of Rac1 and Rac2 significantly delays or abrogates disease development. Attenuation of the disease...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Thomas EK,Cancelas JA,Chae HD,Cox AD,Keller PJ,Perrotti D,Neviani P,Druker BJ,Setchell KD,Zheng Y,Harris CE,Williams DA

    更新日期:2007-11-01 00:00:00

  • EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation.

    abstract::The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B cells and targeted by somatic mutations in B cell lymphomas. Here, we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent ch...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Béguelin W,Popovic R,Teater M,Jiang Y,Bunting KL,Rosen M,Shen H,Yang SN,Wang L,Ezponda T,Martinez-Garcia E,Zhang H,Zheng Y,Verma SK,McCabe MT,Ott HM,Van Aller GS,Kruger RG,Liu Y,McHugh CF,Scott DW,Chung YR,Kel

    更新日期:2013-05-13 00:00:00

  • Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis.

    abstract::We identify a new enzymatic activity underlying metastasis in breast cancer and describe its susceptibility to therapeutic inhibition. We show that human prune (h-prune), a phosphoesterase DHH family appertaining protein, has a hitherto unrecognized cyclic nucleotide phosphodiesterase activity effectively suppressed b...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: D'Angelo A,Garzia L,André A,Carotenuto P,Aglio V,Guardiola O,Arrigoni G,Cossu A,Palmieri G,Aravind L,Zollo M

    更新日期:2004-02-01 00:00:00

  • Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and tumor progression without affecting normal growth.

    abstract::Eukaryotic Initiation Factor 6 (eIF6) controls translation by regulating 80S subunit formation. eIF6 is overexpressed in tumors. Here, we demonstrate that eIF6 inactivation delays tumorigenesis and reduces tumor growth in vivo. eIF6(+/-) mice resist to Myc-induced lymphomagenesis and have prolonged tumor-free survival...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Miluzio A,Beugnet A,Grosso S,Brina D,Mancino M,Campaner S,Amati B,de Marco A,Biffo S

    更新日期:2011-06-14 00:00:00

  • Targeting the lncRNA SAMMSON Reveals Metabolic Vulnerability in Melanoma.

    abstract::In a recent study, Leucci et al. report a role for the long non-coding RNA SAMMSON in driving mitochondrial function in melanoma. Targeting SAMMSON, the gene of which is frequently co-amplified with MITF, highlights a new cell-type-specific therapeutic vulnerability in melanoma irrespective of BRAF, NRAS, or p53 statu...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Goding CR

    更新日期:2016-05-09 00:00:00

  • Stressing Out about Cancer Immunotherapy.

    abstract::Stress has long been suspected to negatively influence cancer mortality, yet the molecular mechanisms responsible for this effect have only recently been identified. A new study identifies a stress-induced response in dendritic cells-the activation of the glucocorticoid-inducible transcriptional regulator TSC22D3-as a...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审


    authors: He XY,Ng D,Van Aelst L,Egeblad M

    更新日期:2019-11-11 00:00:00

  • PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress.

    abstract::Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte li...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Vazquez F,Lim JH,Chim H,Bhalla K,Girnun G,Pierce K,Clish CB,Granter SR,Widlund HR,Spiegelman BM,Puigserver P

    更新日期:2013-03-18 00:00:00

  • E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.

    abstract::Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in human malignancies. Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel wi...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Petrocca F,Visone R,Onelli MR,Shah MH,Nicoloso MS,de Martino I,Iliopoulos D,Pilozzi E,Liu CG,Negrini M,Cavazzini L,Volinia S,Alder H,Ruco LP,Baldassarre G,Croce CM,Vecchione A

    更新日期:2008-03-01 00:00:00

  • Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes.

    abstract::Hepatocellular carcinoma (HCC), the fastest rising cancer in the United States and increasing in Europe, often occurs with nonalcoholic steatohepatitis (NASH). Mechanisms underlying NASH and NASH-induced HCC are largely unknown. We developed a mouse model recapitulating key features of human metabolic syndrome, NASH, ...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Wolf MJ,Adili A,Piotrowitz K,Abdullah Z,Boege Y,Stemmer K,Ringelhan M,Simonavicius N,Egger M,Wohlleber D,Lorentzen A,Einer C,Schulz S,Clavel T,Protzer U,Thiele C,Zischka H,Moch H,Tschöp M,Tumanov AV,Haller D,Ung

    更新日期:2014-10-13 00:00:00

  • Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations.

    abstract::8p11 myeloproliferative syndrome (EMS) is a hematopoietic stem cell disorder characterized by myeloid hyperplasia and non-Hodgkin's lymphoma with chromosomal translocations fusing several genes, most commonly ZNF198, to fibroblast growth factor receptor-1 (FGFR1). However, patients with BCR-FGFR1 fusion present with t...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Roumiantsev S,Krause DS,Neumann CA,Dimitri CA,Asiedu F,Cross NC,Van Etten RA

    更新日期:2004-03-01 00:00:00

  • CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages.

    abstract::During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: DeNardo DG,Barreto JB,Andreu P,Vasquez L,Tawfik D,Kolhatkar N,Coussens LM

    更新日期:2009-08-04 00:00:00

  • A Systematic Framework to Rapidly Obtain Data on Patients with Cancer and COVID-19: CCC19 Governance, Protocol, and Quality Assurance.

    abstract::When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 instit...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: COVID-19 and Cancer Consortium. Electronic address:,COVID-19 and Cancer Consortium.

    更新日期:2020-12-14 00:00:00

  • A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2.

    abstract::Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. Here, we identify and validate a prognostic gene expression signature correlating with survival in a series of microdissect...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Mok SC,Bonome T,Vathipadiekal V,Bell A,Johnson ME,Wong KK,Park DC,Hao K,Yip DK,Donninger H,Ozbun L,Samimi G,Brady J,Randonovich M,Pise-Masison CA,Barrett JC,Wong WH,Welch WR,Berkowitz RS,Birrer MJ

    更新日期:2009-12-08 00:00:00

  • Her 2 in 1.

    abstract::In this issue of Cancer Cell, Park et al. demonstrate that anti-erbB2 antibody primes adaptive immunity for increased tumor clearance and suggest that chemotherapy may in fact interfere with this process. ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Smyth MJ,Stagg J

    更新日期:2010-08-09 00:00:00

  • Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.

    abstract::Polymorphonuclear neutrophils (PMNs) are largely considered to foster cancer development despite wielding an arsenal of cytotoxic agents. Using a mouse model of PTEN-deficient uterine cancer, we describe a surprising inhibitory role for PMNs in epithelial carcinogenesis. By inducing tumor cell detachment from the base...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Blaisdell A,Crequer A,Columbus D,Daikoku T,Mittal K,Dey SK,Erlebacher A

    更新日期:2015-12-14 00:00:00

  • Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation.

    abstract::It is believed that Mdm2 suppresses p53 in two ways: transcriptional inhibition by direct binding, and degradation via its E3 ligase activity. To study these functions physiologically, we generated mice bearing a single-residue substitution (C462A) abolishing the E3 function without affecting p53 binding. Unexpectedly...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Itahana K,Mao H,Jin A,Itahana Y,Clegg HV,Lindström MS,Bhat KP,Godfrey VL,Evan GI,Zhang Y

    更新日期:2007-10-01 00:00:00

  • Inhibition of the Mitochondrial Protease ClpP as a Therapeutic Strategy for Human Acute Myeloid Leukemia.

    abstract::From an shRNA screen, we identified ClpP as a member of the mitochondrial proteome whose knockdown reduced the viability of K562 leukemic cells. Expression of this mitochondrial protease that has structural similarity to the cytoplasmic proteosome is increased in leukemic cells from approximately half of all patients ...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Cole A,Wang Z,Coyaud E,Voisin V,Gronda M,Jitkova Y,Mattson R,Hurren R,Babovic S,Maclean N,Restall I,Wang X,Jeyaraju DV,Sukhai MA,Prabha S,Bashir S,Ramakrishnan A,Leung E,Qia YH,Zhang N,Combes KR,Ketela T,Lin F

    更新日期:2015-06-08 00:00:00

  • The Platelet Lifeline to Cancer: Challenges and Opportunities.

    abstract::Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of tumorigenesis including tumor growth, tumor cell extravasation, and metastasis. Additionally, thrombocytosis in cancer patients is associated with adverse patient...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审


    authors: Haemmerle M,Stone RL,Menter DG,Afshar-Kharghan V,Sood AK

    更新日期:2018-06-11 00:00:00