Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases.
Van den Eynden, G
Van Rheenen, J
Van Laere, S
MetadataShow full item record
The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.
Version of record
Actin-Related Protein 2-3 Complex
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Ductal, Breast
Drug Resistance, Neoplasm
Gene Knockdown Techniques
Medicine (RMH Smith Cunningham)
License start date
Nat Med, 22 (11), pp. 1294 - 1302
Showing items related by title, author, creator and subject.
Viski, C; König, C; Kijewska, M; Mogler, C; Isacke, CM; Augustin, HGMetastasis is a multistep process that is critically dependent on the interaction of metastasizing tumor cells with cells in the local microenvironment. Within this tumor stroma, vessel-associated pericytes and myofibroblasts ...
Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma. Lee, JY; Garcia-Murillas, I; Cutts, RJ; De Castro, DG; Grove, L; Hurley, T; Wang, F; Nutting, C; Newbold, K; Harrington, K; Turner, N; Bhide, S (2017-09-05)BACKGROUND: Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for ...
Sud, A; Thomsen, H; Sundquist, K; Houlston, RS; Hemminki, K (2017-05-10)Purpose Although advances in Hodgkin lymphoma (HL) treatment have led to improved disease-free survival, this has been accompanied by an increased risk of second cancers. We sought to quantify the second cancer risks and ...