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. 2015 Feb 11;6:6139. doi: 10.1038/ncomms7139

Figure 7. Temporally constrained inhibition of SFK signalling can target a vulnerable state during chemotherapy-induced cellular transition.

Figure 7

(a) Representative H&E and IHC of activated caspase-3 in human taxane-refractory tumour explant treated with docetaxel or a combination of docetaxel and dasatinib. Histogram shows IHC score quantification of activated caspase-3 (N=6, **P<0.01). Data shown are mean±s.e.m. from independent replicates. Scale bar, 100 μm (b) Schematic shows the treatment of parent drug-naive cells with cytotoxic chemotherapy (taxane) confers phenotypic plasticity transitioning the population towards a transient drug-tolerant state, arising through clustering of CD44 and CD24 in lipid rafts, HCK activation and suppression of proapoptotic signalling via nuclear translocation. This transient state is vulnerable to inhibition of SFK using kinase inhibitors, leading to apoptosis. The same SFK inhibitors have no effect on parent cells.