Several studies have explored the potential of targeting tumor angiogenesis in cancer treatment. Anti-angiogenesis monotherapy, which reduces blood vessel numbers, may still hold some promise in cancer treatment, but thus far it has only provided a modest effect on overall survival benefits. When combined with standard chemotherapies, some significant improvements in cancer therapy have been reported. However, anti-angiogenesis therapies can have undesirable effects, including the induction of tumor hypoxia and reduction of delivery of chemotherapeutic drugs. Interestingly, anti-angiogenic drugs, such as bevacizumab, when used at lower doses, can actually induce vascular normalization (that is, they improve blood vessel function and flow) and potentially enhance co-administrated chemotherapeutic drug delivery. Unfortunately, vascular normalization is a difficult approach to apply in clinical settings. Thus, there is an urgent need to explore new approaches for modulating the tumor vasculature. Here, we explore how vascular promotion strategies (which enhance blood vessel numbers and leakiness) may be optimized for combination therapies as an alternative option for cancer treatment.
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