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. 2023 Mar 6;24(5):5014. doi: 10.3390/ijms24055014

Figure 3.

Figure 3

Molecular mechanisms of ganetespib. HSP90 increases the expression of IGF-1 [91,92], EGFR [72], HER [69,70,71], MET [58,59,80], ER [69], and cytokine receptors. Activation of IGF-1R and EGF stimulates PI3K/Akt/NF-κB and Raf/MEK/ERK signaling, respectively [85]. JAK/STAT3 signaling is enhanced by cytokine receptor activation [93]. Ubiquitinated degradation of the inhibitor of NF-κB (IκB), nuclear translocation of NF-κB, ERK, and STAT3 stimulate gene expression of mediators that increase tumorigenesis. Ganetespib-mediated inhibition of HSP90 leads to the suppression of these signaling mechanisms and anticancer effects.