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. 2023 Mar 13;128(12):2150–2162. doi: 10.1038/s41416-023-02221-1

Fig. 3. A schematic representation of most frequently observed PI3K resistance mechanisms.

Fig. 3

Resistance can occur either by bypass signalling pathways activation, PTEN loss with subsequent build-up of PIP3 or acquisition/evolution of alternative driver mechanisms such as receptor tyrosine kinase (RTK) dysregulation, mutations activating pathway genes in MAPK pathway (such as KRAS), Cell Cycle dysregulation, upregulation of growth factor receptors or gene fusions. Regardless of the predominant mechanism the final effect is cancer cell survival and proliferation even in presence of effective PI3K inhibition. PI3K phosphoinositide 3-kinase, RTK receptor tyrosine kinase, GPCR: G protein-coupled receptor, PIP2 phosphatidylinositol 4, 5 bisphosphate, PIP3 phosphatidylinositol 3, 4, 5 trisphosphate, KRAS Kirsten rat sarcoma virus, ESR1 oestrogen receptor 1. Created with Biorender.com (accessed on 9th December 2022).