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Comment
. 2016 Jul;29(4):401-3.
doi: 10.1111/pcmr.12486.

Breaking BRAF(V600E)-drug resistance by stressing mitochondria

Chi Luo, Pere Puigserver, Hans R Widlund  1
Affiliations
Comment

Breaking BRAF(V600E)-drug resistance by stressing mitochondria

Chi Luo et al. Pigment Cell Melanoma Res. 2016 Jul.
No abstract available

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Figures

Figure 1
Figure 1. Suppression of mitochondrial biogenesis sensitizes melanoma cells to MAPK inhibition
Whereas BRAF(V600E) melanoma cells with high basal level of mitochondrial biogenesis show an increased sensitivity to MAPK inhibition, those that harbor lower level of mitochondria are intrinsically resistant to MAPK blockage. Upon treatment with BRAF inhibitors, the resistant cells become slow-cycling. Concomitantly, slow-cycling resistant cells elevate their mitochondrial biogenesis as mediated by the nuclear-encoded TFAM and TRAP1, leading to the expansion of mitochondrial genome and enhanced mitochondrial protein folding. Consequently, suppression of mitochondrial biogenesis such as by abrogating the mitochondrial protein folding with the HSP90 inhibitor gamitrinib significantly reduces tumor bioenergetics, and also enhances the efficacy of BRAF-targeted inhibitors.
See this image and copyright information in PMC

Comment on

  • Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors.
    Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, Chae YC, Xu X, Choi H, Dimwamwa E, Ope O, Shannan B, Basu D, Zhang D, Guha M, Xiao M, Randell S, Sproesser K, Xu W, Liu J, Karakousis GC, Schuchter LM, Gangadhar TC, Amaravadi RK, Gu M, Xu C, Ghosh A, Xu W, Tian T, Zhang J, Zha S, Liu Q, Brafford P, Weeraratna A, Davies MA, Wargo JA, Avadhani NG, Lu Y, Mills GB, Altieri DC, Flaherty KT, Herlyn M. Zhang G, et al. J Clin Invest. 2016 May 2;126(5):1834-56. doi: 10.1172/JCI82661. Epub 2016 Apr 4. J Clin Invest. 2016. PMID: 27043285 Free PMC article.

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