Clinical validation of prospective liquid biopsy monitoring in patients with wild-type RAS metastatic colorectal cancer treated with FOLFIRI-cetuximab Academic Article uri icon


MeSH Major

  • Antineoplastic Agents, Immunological
  • Antineoplastic Combined Chemotherapy Protocols
  • Camptothecin
  • Cetuximab
  • Colorectal Neoplasms
  • DNA Mutational Analysis
  • ras Proteins


  • Cancer genomics and translational medicine rely on the molecular profiling of patient's tumor obtained during surgery or biopsy. Alternatively, blood is a less invasive source of tumor DNA shed, amongst other ways, as cell-free DNA (cfDNA). Highly-sensitive assays capable to detect cancer genetic events from patient's blood plasma became popularly known as liquid biopsy (LqB). Importantly, retrospective studies including small number of selected patients with metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapy have shown LqB capable to detect the acquired clonal mutations in RAS genes leading to therapy resistance. However, the usefulness of LqB in the real-life clinical monitoring of these patients still lack additional validation on controlled studies. In this context, we designed a prospective LqB clinical trial to monitor newly diagnosed KRAS wild-type (wt) mCRC patients who received a standard FOLFIRI-cetuximab regimen. We used BEAMing technique for evaluate cfDNA mutations in KRAS, NRAS, BRAF, and PIK3CA in twenty-five patients during a 2-y period. A total of 2,178 cfDNA mutation analyses were performed and we observed that: a) continued wt circulating status was correlated with a prolonged response; b) smoldering increases in mutant cfDNA were correlated with acquired resistance; while c) mutation upsurge/explosion anticipated a remarkable clinical deterioration. The current study provides evidences, obtained for the first time in an unbiased and prospective manner, that reinforces the utility of LqB for monitoring mCRC patients.

publication date

  • January 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5471055

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.13311

PubMed ID

  • 27852040

Additional Document Info

start page

  • 35289

end page

  • 35300


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