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Comment
. 2021 Feb 15;27(4):913-915.
doi: 10.1158/1078-0432.CCR-20-3914. Epub 2020 Dec 16.

Transcription Strikes Back: Clinical Utility of Lung Adenocarcinoma Subtypes

Ferdinandos Skoulidis  1
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Transcription Strikes Back: Clinical Utility of Lung Adenocarcinoma Subtypes

Ferdinandos Skoulidis. Clin Cancer Res. .

Abstract

Using transcriptional profiling, three robust subtypes of nonsquamous non-small cell lung cancer were defined, independently of initiating oncogenic driver events. Subtype-specific differential sensitivity to MEK1/2 inhibitors was reported and an interaction between the mucinous subtype, STK11/LKB1 genomic alterations, and inferior clinical outcomes with atezolizumab in the OAK clinical trial was identified.See related article by Daemen et al., p. 1162.

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References

    1. Daemen A, Cooper J, Myrta S, Wongchenko MJ, Lin E, Long JE, et al. Transcriptional subtypes resolve tumor heterogeneity and identify vulnerabilities to MEK inhibition in lung adenocarcinoma. Clin Cancer Res. 2021;27:1162–73.
    1. Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, et al. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov. 2015;5:860–77.
    1. Singh A, Daemen A, Nickles D, Jeon SM, Foreman O, Sudini K, et al. NRF2 activation promotes aggressive lung cancer and associates with poor clinical outcomes. Clin Cancer Res. 2020.
    1. Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8:822–35.
    1. Skoulidis F, Arbour KC, Hellmann MD, Patil PD, Marmarelis ME, Awad MM, et al. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer. J Clin Oncol. 2019;37.

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