Assessing metastasis risk after pre-operative anti-angiogenic therapy

Abstract

Anti-angiogenic drugs are approved for the treatment of several cancer types, generally in the inoperable locally advanced or metastatic setting and in combination with other anti‐cancer agents. Recent clinical studies also suggest that anti‐angiogenic drugs can be useful in the pre‐operative (neoadjuvant) setting, by facilitating the shrinkage of the primary tumour and its surgical resection. However, the effects of neoadjuvant anti‐angiogenic therapy on the ability of tumours to form distant metastases are unclear. In this issue of EMBO Molecular Medicine, Ebos et al (2014) present carefully performed pre-clinical studies in mice that analyse the effects of pre-operative anti-angiogenic therapy on tumour metastasis and survival.

Figure 1. Testing neoadjuvant anti-angiogenic therapies in an excisional breast cancer model

(A) A human breast cancer cell line with metastatic capability is genetically modified with a luciferase construct to allow in vivo tracing. Primary tumour growth is initiated by orthotopically transplanting the cancer cells in the mammary fat pad of severe combined immunodeficient (SCID) mice. Established tumours are then treated with specific drug combinations, including anti-angiogenic agents. The primary tumours are removed and the subsequent formation of metastases is monitored by measuring luciferase activity. (B) The therapeutic benefits of the distinct drugs—alone or in combination, and at different dosage regimens—on the primary tumours and post-surgical metastases are shown (for details on dosage regimens and quantitative data, refer to Ebos et al (2014)). Note that Ebos et al (2014) investigated several tumour models; for the sake of simplicity, only the breast cancer model is exemplified in the figure. LDC, low-dose chemotherapy (cyclophosphamide plus 5-fluorouracil).