ABCA4 and neoplasm: Current formulated hypotheses regarding resistance mechanisms are (i) changes in the tumor microenvironment leading to decreased penetration of the drug agent into the tumor cell, (ii) some deficiencies in the internalization pathways adapting resistance to payloads, (iii) down-regulation of antigens [92,172], and (iv) induction of the active efflux of cytotoxic payloads that are transported by ATP-binding cassette transporter proteins, like multidrug resistance protein 1 [173].