Aberrant post-translational modifications in endosomal trafficking are potential therapeutic targets to avert therapy resistance in solid cancers Dysregulation of PTM-regulated endosomal interactions presents an opportunity to block oncogenic signalling from multiple receptors by targeting common trafficking pathways

Drugs targeting a single TK/RTK in the treatment of solid cancers has not had the same success seen in blood cancers. This is, in part, due to acquired resistance in solid cancers arising from a range of mechanisms including the upregulation of compensatory RTK signalling. Rather than attempting to inhibit individual compensatory RTK-requiring knowledge of which RTKs are upregulated in any given tumour-strategies to universally inhibit signalling from multiple RTKs may represent an effective alternative. Endosomal trafficking of RTKs is a common conduit that can regulate signalling from multiple RTKs simultaneously. As such, we posit that targeting endosomal trafficking-in particular, aberrant post-translational modifications in cancers that contribute to dysregulated endosomal trafficking-could inhibit oncogenic signalling driven by multiple RTKs and pave the way for the development of a novel class of inhibitors that shift the trafficking of RTKs to inhibit tumour growth.

Automated summary

Targeting a single TK/RTK in solid cancer treatment has not been as successful as in blood cancers, partly due to acquired resistance and upregulation of compensatory RTK signaling. Instead of inhibiting individual compensatory RTKs, universally inhibiting signaling from multiple RTKs may prove to be a more effective approach.