RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study
Open accessAbstract
Liquid biopsies have shown that, in RAS mutant colorectal cancer, the conversion to RAS wild-type * status during the course of the disease is a frequent event, supporting the concept that the evolutionary landscape of colorectal cancer can lead to an unexpected negative selection of RAS mutant clones. The aim of the present study was to clarify whether the negative selection of RAS mutation in plasma might be drug-dependent. For this purpose, we used liquid biopsy to compare the rate of conversion from RAS mutant to RAS wild-type * in two groups of originally RAS mutant mCRC patients: the first treated with chemotherapy alone, while the second was treated with chemotherapy combined with bevacizumab. Serial liquid biopsies were performed at 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4) after starting first line treatments. We found that the only independent variable significantly associated to RAS status conversion was the use of bevacizumab. RAS conversion was not found associated to tumor burden reduction, although bevacizumab-treated patients who converted to RAS wild-type * had a significantly longer PFS compared to patients who remained RAS mutant. The appearance of a “RAS wild-type * window”, mainly in bevacizumab-treated patients, might present them as candidates for second line treatment with anti-EGFR, which was otherwise precluded.
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Bevacizumab use emerged as a significant factor in facilitating NeoRAS WT shift, and patients achieving RAS WT status demonstrated improved mPFS when treated with bevacizumab.
“Bevacizumab use emerged as a significant factor in facilitating the NeoRAS WT shift, and patients achieving RAS WT status demonstrated improved median progression-free survival (mPFS) when treated with bevacizumab.”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [54]
Patients treated with chemotherapy in combination with bevacizumab exhibited a higher rate of RAS conversion compared to those receiving chemotherapy alone.
“Importantly, patients treated with chemotherapy in combination with bevacizumab exhibited a higher rate of RAS conversion compared to those receiving chemotherapy alone [54].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [54]
In a study by Chiara Nicolazzo et al., 43 of 72 patients (60%) with initial RAS mutations achieved WT status over 3-12 months, while 29 patients (40%) retained RAS-mutant profile, independent of mutation subtype.
“In a study by Chiara Nicolazzo et al., 43 of 72 patients (60%) with initial RAS mutations achieved WT status over 3–12 months, while 29 patients (40%) retained their RAS-mutant profile, independent of mutation subtype.”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [54]
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- Authors
- Nicolazzo, C., Belardinilli, F., Vestri, A., Magri, V., De Renzi, G., De Meo, M., Caponnetto, S., Di Nicolantonio, F., Cortesi, E., Giannini, G., & Gazzaniga, P.
- Affiliations
- Sapienza University of Rome (IT)
- Department of Molecular Medicine, Sapienza University of Rome, 00185 Roma, Italy
- Department of Oncology, University of Turin, 10124 Torino, Italy
- Corresponding author
- Gazzaniga, Paola
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2022-02-04
- Volume
- 14
- Issue
- 3
- Pages
- 802
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8833999
- OpenAlex
- W4210596686
- Cited by
- 21
- References
- 31
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 7
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- Funders
- Sapienza University of Rome (RM11916B31436754)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- metastatic colorectal cancer, bevacizumab, liquid biopsy, plasma circulating tumor DNA, progression-free survival, anti-EGFR therapy, chemotherapy, tumor evolution
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