Twenty years after: the beautiful hypothesis and the ugly facts

The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels and cancer. Tumors need blood perfusion but there are mounting evidences that angiogenesis alone does not explain it in all the neoplasms. In this editorial, for a special issue on tumor and vessels published in the Chinese Journal of Cancer, we briefly introduce the history of the evidences that solid tumors can sometimes obtain blood perfusion by alternative approaches other than sprouting angiogenesis, i.e., vessel co-option and vasculogenic mimicry. This editorial provides also the links to several most recently published discoveries and hypotheses on tumor interaction with blood vessels.