A hypothesis to explain the lower potency of CTX-MMAE on the PANC-1 tumour in vivo, despite its higher EGFR expression and greater in vitro sensitivity, is that the greater abundance of high-affinity receptors proximal to afferent microvessels would deplete the inward flux of ADC, constituting a ‘binding site barrier’ (Fig. 5fi) that would reduce tumour penetration of CTX-MMAE.32 Although the PANC-1 tumour cells near microvessels would be killed efficiently by CTX-MMAE, those at a greater distance from microvessels would experience lower ADC exposure, potentially escaping killing (Fig. 5fii). Here, EGFR is linked to neoplasm.