HIF1A and neoplasm: Tumor microenvironment complexities, such as desmoplasia in pancreatic cancer impeding penetration (diffusion coefficients 10–8–10–9 cm2/s vs. 10–6 in normal tissues) and hypoxia-induced resistance (HIF-1α upregulation decreasing efficacy by 2–3-fold), necessitate strategies like stroma-modulating adjuncts (e.g., hyaluronidase co-delivery increasing permeability by 4-fold) [70].