Potential causes of intrinsic resistance include the following: differential expression of the VEGF pro- and anti-angiogenic isoforms, VEGF and VEGFR polymorphisms, limited penetration of antibodies into the tumour mass and pre-existing tumour microenvironment which results in a lack of effect such as dependence on vessel co-option, vessels that are well differentiated, or stimulated by pathways other than VEGF will also be resistant (Bergers & Hanahan, 2008; Donnem et al, 2013; Welti et al, 2013; Stapor et al, 2014). This evidence concerns the gene KDR and neoplasm.