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KRASness and PIK3CAness in Patients with Advanced Colorectal Cancer: Outcome after Treatment with Early-Phase Trials with Targeted Pathway Inhibitors

Author

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  • Ignacio Garrido-Laguna
  • David S Hong
  • Filip Janku
  • Ly M Nguyen
  • Gerald S Falchook
  • Siqing Fu
  • Jenifer J Wheler
  • Rajyalakshmi Luthra
  • Aung Naing
  • Xuemei Wang
  • Razelle Kurzrock

Abstract

Purpose: To evaluate clinicopathologic and molecular features of patients with metastatic colorectal cancer (mCRC) and their outcomes in early-phase trials using pathway-targeting agents. Patients and Methods: We analyzed characteristics of 238 patients with mCRC referred to the phase 1 trials unit at MD Anderson Cancer Center. KRAS, PIK3CA and BRAF status were tested using PCR-based DNA sequencing. Results: Fifty-one percent of patients harbored KRAS mutations; 15% had PIK3CA mutations. In the multivariate regression model for clinical characteristics KRAS mutations were associated with an increased incidence of lung and bone metastases and decreased incidence of adrenal metastases; PIK3CA mutations were marginally correlated with mucinous tumors (p = 0.05). In the univariate analysis, KRAS and PIK3CA mutations were strongly associated. Advanced Duke's stage (p

Suggested Citation

  • Ignacio Garrido-Laguna & David S Hong & Filip Janku & Ly M Nguyen & Gerald S Falchook & Siqing Fu & Jenifer J Wheler & Rajyalakshmi Luthra & Aung Naing & Xuemei Wang & Razelle Kurzrock, 2012. "KRASness and PIK3CAness in Patients with Advanced Colorectal Cancer: Outcome after Treatment with Early-Phase Trials with Targeted Pathway Inhibitors," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-8, May.
    • Handle: RePEc:plo:pone00:0038033
    DOI: 10.1371/journal.pone.0038033
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    1. Anirudh Prahallad & Chong Sun & Sidong Huang & Federica Di Nicolantonio & Ramon Salazar & Davide Zecchin & Roderick L. Beijersbergen & Alberto Bardelli & René Bernards, 2012. "Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR," Nature, Nature, vol. 483(7387), pages 100-103, March.
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