K. Hellmann
2004
Citations
0
Influential Citations
19
Citations
Journal
Clinical & Experimental Metastasis
Abstract
Drug development is an unpredictable business; new and unexpected indications as well as new and unexpected adverse reactions may emerge years after a drug was first introduced. I make no apology therefore for considering in this review some results which were obtained two to three decades ago and which show that razoxane is not only experimentally, but also clinically active against angiogenesis and metastasis. Even in what are meant to be exhaustive reviews of tumour angiogenesis (and metastasis) pertinent results with razoxane have not been much in evidence. This might be more readily understood if verification of the received (if simplistic) wisdom that destruction of the tumour neovasculature or prevention of its appearance will destroy cancer, had proven unambiguously successful in the clinic. The reality is, however, that there has yet to be a convincing demonstration from any one of the large number of agents tested for antiangiogenic activity, that clinically effective and worthwhile results can be obtained. A recent review by Kerbel and Folkman [1] illustrates this very clearly by the paucity of clinical results that they were able to examine now some 31 years after Folkman speculated on the therapeutic implications of inhibition of tumour angiogenesis [2]. It also comes some 32 years after we first demonstrated that ‘normalization’ of the abnormal tumour neovasculature by razoxane prevented metastasis [3] thereby converting a malignant into a quasibenign tumour – a disease modifying activity – previously unknown. Apart from pointing out why anti-angiogenesis should work in cancer patients and why it has not – as yet, Kerbel and Folkman also call attention to a study by Rakesh Jain [4]. This ‘study’ which claims to have discovered a new paradigm for combination therapy – ‘through normalization of the tumour vasculature with anti-angiogenic therapy’ is not supported by any new experimental or clinical results. The paradigm may not be new [5, 41] but the admission may be a first: that vascular normalization could be significant for cancer therapy. This, and the wide therapeutic potential of normalization of a pathological vasculature is something