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

Abstract:

: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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

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

doi

10.1016/j.ccell.2014.11.005

subject

Has Abstract

pub_date

2014-12-08 00:00:00

pages

880-895

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(14)00456-5

journal_volume

26

pub_type

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