TY  - JOUR
AU  - Srivastava, Kshitij
AU  - Hu, Junhao
AU  - Korn, Claudia
AU  - Savant, Soniya
AU  - Teichert, Martin
AU  - Kapel, Stephanie
AU  - Jugold, Manfred
AU  - Besemfelder, Eva
AU  - Thomas, Markus
AU  - Pasparakis, Manolis
AU  - Augustin, Hellmut
TI  - Postsurgical adjuvant tumor therapy by combining anti-angiopoietin-2 and metronomic chemotherapy limits metastatic growth.
JO  - Cancer cell
VL  - 26
IS  - 6
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2017-04385
SP  - 880 - 895
PY  - 2014
AB  - 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.
KW  - Adjuvants, Pharmaceutic (NLM Chemicals)
KW  - Angiogenesis Inhibitors (NLM Chemicals)
KW  - Paclitaxel (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25490450
DO  - DOI:10.1016/j.ccell.2014.11.005
UR  - https://inrepo02.dkfz.de/record/128368
ER  -