RAS Mutational Status in Advanced Colorectal Adenocarcinoma Treated With Anti-angiogenics: Preliminary Experience With Liquid Biopsy

In Vivo. 2021 Sep-Oct;35(5):2841-2844. doi: 10.21873/invivo.12571.


Aim: To determinate molecular changes in the downstream epidermal growth factor receptor signaling pathway using serial liquid biopsies in patients with metastatic colorectal tumors (mCRC) under anti-angiogenic treatment.

Patients and methods: Determination of RAS mutation in primary tissue samples from colorectal tumors was performed in the 23 patients included in the study at diagnosis using quantitative-polymerase chain reaction. Sequential mutations were studied in circulating tumor (ct) DNA obtained from plasma samples.

Results: Twenty-three patients with RAS-mutated primary tumors were included. In the first ctDNA determination, 17 of these patients were found to have wild-type RAS status. Remarkably, three out of these 17 wild-type cases changed to RAS-mutated in subsequent ctDNA assays.

Conclusion: Serial liquid biopsies in patients with mCRC might be a useful tool for identifying changes in the RAS mutation status in patients who had undergone previous anti-angiogenic therapy. The understanding of these changes might help to better define the landscape of mCRC and be the path to future randomized studies.

Keywords: Colorectal cancer; RAS mutations; anti-angiogenic therapies; circulating tumor DNA; liquid biopsy.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / genetics
  • Circulating Tumor DNA* / genetics
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Humans
  • Liquid Biopsy
  • Mutation


  • Circulating Tumor DNA