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Comment
. 2019 Jun;5(6):327-329.
doi: 10.1016/j.trecan.2019.04.003. Epub 2019 May 7.

Dual Targeting of Autophagy and MEK in KRAS Mutant Cancer

Hongyun Zhao  1 , Bin Zheng  2
Affiliations
Comment

Dual Targeting of Autophagy and MEK in KRAS Mutant Cancer

Hongyun Zhao et al. Trends Cancer. 2019 Jun.

Abstract

In two recent articles, Kinsey et al. (Nature Medicine 2019;25:620-627) and Bryant et al. (Nature Medicine 2019;25:628-640) reported that inhibition of MEK-ERK signaling in KRAS-mutated cancers induced autophagic flux, presumably as a metabolic adaptation mechanism. Importantly, they demonstrated that autophagy blockade via chloroquine (CQ) or hydroxychloroquine (HCQ) enhanced the efficacy of MEK-ERK inhibition in various preclinical models of KRAS-driven cancers, providing a rational basis for future clinical evaluation of this combination therapy.

Keywords: AMPK; KRAS; MEK inhibitor; autophagy; metabolism.

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  • Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers.
    Kinsey CG, Camolotto SA, Boespflug AM, Guillen KP, Foth M, Truong A, Schuman SS, Shea JE, Seipp MT, Yap JT, Burrell LD, Lum DH, Whisenant JR, Gilcrease GW 3rd, Cavalieri CC, Rehbein KM, Cutler SL, Affolter KE, Welm AL, Welm BE, Scaife CL, Snyder EL, McMahon M. Kinsey CG, et al. Nat Med. 2019 Apr;25(4):620-627. doi: 10.1038/s41591-019-0367-9. Epub 2019 Mar 4. Nat Med. 2019. PMID: 30833748 Free PMC article.
  • Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer.
    Bryant KL, Stalnecker CA, Zeitouni D, Klomp JE, Peng S, Tikunov AP, Gunda V, Pierobon M, Waters AM, George SD, Tomar G, Papke B, Hobbs GA, Yan L, Hayes TK, Diehl JN, Goode GD, Chaika NV, Wang Y, Zhang GF, Witkiewicz AK, Knudsen ES, Petricoin EF 3rd, Singh PK, Macdonald JM, Tran NL, Lyssiotis CA, Ying H, Kimmelman AC, Cox AD, Der CJ. Bryant KL, et al. Nat Med. 2019 Apr;25(4):628-640. doi: 10.1038/s41591-019-0368-8. Epub 2019 Mar 4. Nat Med. 2019. PMID: 30833752 Free PMC article.

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