Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer (original) (raw)

References

  1. Ciardiello, F. & Tortora, G. EGFR antagonists in cancer treatment. N. Engl. J. Med. 358, 1160–1174 (2008)
    Article CAS PubMed Google Scholar
  2. Karapetis, C. S. et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359, 1757–1765 (2008)
    Article CAS PubMed Google Scholar
  3. Wheeler, D. L. et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene 27, 3944–3956 (2008)
    Article CAS PubMed PubMed Central Google Scholar
  4. Benavente, S. et al. Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells. Clin. Cancer Res. 15, 1585–1592 (2009)
    Article CAS PubMed PubMed Central Google Scholar
  5. Li, C., Iida, M., Dunn, E. F., Ghia, A. J. & Wheeler, D. L. Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene 28, 3801–3813 (2009)
    Article CAS PubMed PubMed Central Google Scholar
  6. Hatakeyama, H. et al. Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma. PLoS ONE 5, e12702 (2010)
    Article ADS PubMed PubMed Central Google Scholar
  7. Yonesaka, K. et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci. Transl. Med. 3, 99ra86 (2011)
    Article PubMed PubMed Central Google Scholar
  8. Montagut, C. et al. Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. Nature Med. 18, 221–223 (2012)
    Article CAS PubMed Google Scholar
  9. Moroni, M. et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol. 6, 279–286 (2005)
    Article CAS PubMed Google Scholar
  10. De Roock, W. et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 11, 753–762 (2010)
    Article CAS PubMed Google Scholar
  11. Diehl, F. et al. Circulating mutant DNA to assess tumor dynamics. Nature Med. 14, 985–990 (2008)
    Article CAS ADS PubMed Google Scholar
  12. Di Nicolantonio, F. et al. Replacement of normal with mutant alleles in the genome of normal human cells unveils mutation-specific drug responses. Proc. Natl Acad. Sci. USA 105, 20864–20869 (2008)
    Article CAS ADS PubMed PubMed Central Google Scholar
  13. Bardelli, A. & Siena, S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J. Clin. Oncol. 28, 1254–1261 (2010)
    Article CAS PubMed Google Scholar
  14. Van Cutsem, E. et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med. 360, 1408–1417 (2009)
    Article CAS PubMed Google Scholar
  15. Amado, R. G. et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26, 1626–1634 (2008)
    Article CAS PubMed Google Scholar
  16. Janne, P. A. Challenges of detecting EGFR T790M in gefitinib/erlotinib-resistant tumours. Lung Cancer 60, (suppl. 2)S3–S9 (2008)
    Article PubMed Google Scholar
  17. Engelman, J. A. et al. Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer. J. Clin. Invest. 116, 2695–2706 (2006)
    Article CAS PubMed PubMed Central Google Scholar
  18. Arcila, M. E. et al. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin. Cancer Res. 17, 1169–1180 (2011)
    Article CAS PubMed PubMed Central Google Scholar
  19. Molinari, F. et al. Increased detection sensitivity for KRAS mutations enhances the prediction of anti-EGFR monoclonal antibody resistance in metastatic colorectal cancer. Clin. Cancer Res. 17, 4901–4914 (2011)
    Article CAS PubMed Google Scholar
  20. Whitehead, R. H., Macrae, F. A., St John, D. J. & Ma, J. A colon cancer cell line (LIM1215) derived from a patient with inherited nonpolyposis colorectal cancer. J. Natl. Cancer Inst. 74, 759–765 (1985)
    CAS PubMed Google Scholar
  21. Smith, G. et al. Activating K-Ras mutations outwith ‘hotspot’ codons in sporadic colorectal tumours - implications for personalised cancer medicine. Br. J. Cancer 102, 693–703 (2010)
    Article CAS PubMed PubMed Central Google Scholar

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Acknowledgements

We are particularly indebted to S. Lamba for generating the KRAS(G12R) knock-in in Lim1215 cells. We thank C. Cancelliere and S. Destefanis for technical assistance. We thank S. Arena, M. Russo and D. Zecchin for critically reading the manuscript. We also thank A. Heguy, A. Viale, N. Socci and M. Pirun for assistance with analysis of next generation sequencing data. This work was supported by European Union Seventh Framework Programme, grant 259015 COLTHERES (A.B. and S.S.); Associazione Italiana per la Ricerca sul Cancro (AIRC) 2010 Special Program Molecular Clinical Oncology 5 × 1000, project 9970 (A.B. and S.S.); Regione Piemonte (A.B. and F.D.N.); Fondazione Piemontese per la Ricerca sul Cancro (FPRC) Intramural Grant, 5xmille 2008, ONLUS (A.B. and F.D.N.); AIRC MFAG 11349 (F.D.N.); Oncologia Ca’ Granda ONLUS (OCGO) (S.S.); Mr William H. Goodwin and Mrs Alice Goodwin and the Commonwealth Foundation for Cancer Research; the Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center (D.S.); the Society of MSKCC (M.W.); the National Institutes of Health (D.S.); the Beene Foundation (D.S.) and Regione Lombardia and Ministerio Salute grant ‘Gene Mutation Monitoring in mCRC’ (S.S.).

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Author notes

  1. Sandra Misale, Rona Yaeger, Sebastijan Hobor, Elisa Scala and Manickam Janakiraman: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment (IRCC), 10060 Candiolo (Torino), Italy ,
    Sandra Misale, Sebastijan Hobor, Elisa Scala, Michela Buscarino, Giulia Siravegna, Carlo Zanon, Federica Di Nicolantonio & Alberto Bardelli
  2. Department of Oncological Sciences, University of Torino Medical School, 10060 Candiolo (Torino), Italy,
    Sandra Misale, Elisa Scala, Michela Buscarino, Enzo Medico & Alberto Bardelli
  3. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USA
    Rona Yaeger, Andrea Cercek & David Solit
  4. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USA
    Manickam Janakiraman & David Solit
  5. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USA
    David Liska, Chin-Tung Chen & Martin Weiser
  6. Division of Pathology, Ospedale Niguarda Ca’ Granda, 20162 Milano, Italy,
    Emanuele Valtorta, Silvio Veronese & Marcello Gambacorta
  7. Falck Division of Medical Oncology, Ospedale Niguarda Ca’ Granda, 20162 Milano, Italy,
    Roberta Schiavo, Katia Bencardino, Andrea Sartore-Bianchi & Salvatore Siena
  8. Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, 10125 Torino, Italy,
    Margherita Gallicchio & Valentina Boscaro
  9. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USA
    Efsevia Vakiani
  10. Laboratory of Functional Genomics, Institute for Cancer Research and Treatment (IRCC), 10060 Candiolo (Torino), Italy ,
    Enzo Medico
  11. FIRC Institute of Molecular Oncology (IFOM), 20139 Milano, Italy ,
    Federica Di Nicolantonio & Alberto Bardelli

Authors

  1. Sandra Misale
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  2. Rona Yaeger
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  3. Sebastijan Hobor
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  4. Elisa Scala
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  5. Manickam Janakiraman
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  6. David Liska
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  7. Emanuele Valtorta
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  8. Roberta Schiavo
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  9. Michela Buscarino
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  10. Giulia Siravegna
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  11. Katia Bencardino
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  12. Andrea Cercek
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  13. Chin-Tung Chen
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  14. Silvio Veronese
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  15. Carlo Zanon
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  16. Andrea Sartore-Bianchi
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  17. Marcello Gambacorta
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  18. Margherita Gallicchio
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  19. Efsevia Vakiani
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  20. Valentina Boscaro
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  21. Enzo Medico
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  22. Martin Weiser
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  23. Salvatore Siena
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  24. Federica Di Nicolantonio
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  25. David Solit
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  26. Alberto Bardelli
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Contributions

A.B., D.S., S.S. and F.D.N. planned the project and supervised all research. A.B., D.S. and F.D.N. wrote the manuscript. S.M., R.Y., S.H., E.S., M.W. and F.D.N. designed the experiments. A.B. conceived the molecular analysis of plasma samples. S.M., R.Y., S.H., E.S., M.J., D.L., E.V., R.S., M.B., G.S., C.-T.C., S.V., M.G. and V.B. performed the experiments. C.Z., A.S.-B., M.G. and E.M. analysed data. K.B., A.C. and E.V. provided samples for analysis. S.S., D.S. and A.B. devised dual biopsy clinical protocols for EGFR mAb resistant mCRC.

Corresponding authors

Correspondence toDavid Solit or Alberto Bardelli.

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The authors declare no competing financial interests.

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Misale, S., Yaeger, R., Hobor, S. et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer.Nature 486, 532–536 (2012). https://doi.org/10.1038/nature11156

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