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A genetic variant in Rassf1a predicts outcome in mCRC patients treated with cetuximab plus chemotherapy: results from FIRE-3 and JACCRO 05 and 06 trials

The Pharmacogenomics Journal volume 18, pages 43–48 (2018)Cite this article

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Abstract

The Hippo pathway is involved in colorectal cancer (CRC) development and progression. The Hippo regulator Rassf1a is also involved in the Ras signaling cascade. In this work, we tested single nucleotide polymorphisms within Hippo components and their association with outcome in CRC patients treated with cetuximab. Two cohorts treated with cetuximab plus chemotherapy were evaluated (198 RAS wild-type (WT) patients treated with first-line FOLFIRI plus Cetuximab within the FIRE-3 trial and 67 Ras WT patients treated either with first-line mFOLFOX6 or SOX plus Cetuximab). In these two populations, Rassf1a rs2236947 was associated with overall survival (OS), as patients with a CC genotype had significantly longer OS compared with those with CA or AA genotypes. This association was stronger in patients with left-side CRC (hazard ratio (HR): 1.79 (1.01–3.14); P=0.044 and HR: 2.83 (1.14–7.03); P=0.025, for Fire 3 and JACCRO cohorts, respectively). Rassf1a rs2236947 is a promising biomarker for patients treated with cetuximab plus chemotherapy.

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Acknowledgements

Ana Sebio is a recipient of a Juan Rodés contract from the Instituto de Salud Carlos III (JR14/00006). Martin D. Berger received a grant from the Swiss Cancer League (BIL KLS-3334-02-2014) and the Werner and Hedy Berger-Janser Foundation for cancer research. This work was supported in part by an award from the National Cancer Institute (P30CA014089), the Wunderglo Project and the Daniel Butler Research Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Authors and Affiliations

  1. Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    A Sebio, Y Sunakawa, W Zhang, A Parek, D Yang, S Cao, Y Ning, S Stremitzer, S Matsusaka, S Okazaki, A Barzi, M D Berger & H-J Lenz

  2. Medical Oncology Department, Santa Creu i Sant Pau Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain

    A Sebio

  3. Department of Hematology and Oncology, Klinikum der Universitat, University of Munich, Munich, Germany

    S Stintzing & V Heinemann

  4. Department of Medical Oncology, Showa University, Yokohama, Japan

    W Ichikawa & T Takahashi

  5. Department of Clinical Oncology, Kagawa University, Kagawa, Japan

    A Tsuji

  6. Department of Preventive Medicine, Norris Comprehensive Cancer Center; Keck School of Medicine, University of Southern California,

    H-J Lenz

  7. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    H-J Lenz

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  1. A Sebio
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Correspondence to H-J Lenz.

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Sebio, A., Stintzing, S., Heinemann, V. et al. A genetic variant in Rassf1a predicts outcome in mCRC patients treated with cetuximab plus chemotherapy: results from FIRE-3 and JACCRO 05 and 06 trials. Pharmacogenomics J 18, 43–48 (2018). https://doi.org/10.1038/tpj.2016.69

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  • DOI: https://doi.org/10.1038/tpj.2016.69

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