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Comment
. 2023 Jan;29(1):29-30.
doi: 10.1038/s41591-022-02129-y.

Time to hit pause on mitochondria-targeting cancer therapies

Xue Zhang  1   2   3 , Chi V Dang  4   5   6   7
Affiliations
Comment

Time to hit pause on mitochondria-targeting cancer therapies

Xue Zhang et al. Nat Med. 2023 Jan.

Abstract

As another clinical trial of a mitochondria-targeting cancer therapy faces failure, it calls for a thorough re-evaluation of the strategy; the time has come to go from the bedside back to the bench.

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Figures

Fig. 1 |
Fig. 1 |. Targeting metabolism for cancer therapy comes with a cost when the scale is tipped toward intolerable on-target, off-tumor side effects.
In a phase 1 study, Yap et al. have found that the mitochondrial complex 1 inhibitor IACS-010759 is associated with peripheral and optic neuropathy. These toxic side effects necessitate dose-limiting to the point of inadequacy, and hence only modest evidence of enhanced efficacy in patients with cancer.
See this image and copyright information in PMC

Comment on

  • Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials.
    Yap TA, Daver N, Mahendra M, Zhang J, Kamiya-Matsuoka C, Meric-Bernstam F, Kantarjian HM, Ravandi F, Collins ME, Francesco MED, Dumbrava EE, Fu S, Gao S, Gay JP, Gera S, Han J, Hong DS, Jabbour EJ, Ju Z, Karp DD, Lodi A, Molina JR, Baran N, Naing A, Ohanian M, Pant S, Pemmaraju N, Bose P, Piha-Paul SA, Rodon J, Salguero C, Sasaki K, Singh AK, Subbiah V, Tsimberidou AM, Xu QA, Yilmaz M, Zhang Q, Li Y, Bristow CA, Bhattacharjee MB, Tiziani S, Heffernan TP, Vellano CP, Jones P, Heijnen CJ, Kavelaars A, Marszalek JR, Konopleva M. Yap TA, et al. Nat Med. 2023 Jan;29(1):115-126. doi: 10.1038/s41591-022-02103-8. Epub 2023 Jan 19. Nat Med. 2023. PMID: 36658425 Free PMC article. Clinical Trial.

References

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