Why the Therapeutic Impact of RAS Mutation Clearance in Plasma ctDNA Deserves to Be Further Explored in Metastatic Colorectal Cancer

Nicolazzo, Chiara; Belardinilli, Francesca; Caponnetto, S; Gradilone, Angela; Cortesi, Enrico; Giannini, Giuseppe; Gazzaniga, Paola

doi:10.3389/fonc.2019.01414

Cited by 9 publications

(8 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, liquid biopsies have shown the selective pressure of anti-EGFR therapies in patients with RAS-wild-type * colorectal tumors, in that acquired resistance to EGFR blockade is often driven by the emergence of KRAS/NRAS mutations in plasma [18]. More recently, we and others have reported that in RAS mutant mCRC, the conversion to RAS wild-type * status in plasma is a frequent event, ranging from 8% to 70% of cases according to studies [19][20][21][22][23], supporting that the evolutionary landscape of mCRC can lead to an unexpected negative selection of RAS mutant clones. Nevertheless, whether this conversion might depend on the evolutionary pressure induced by anti-VEGF treatments is still under debate.…”

Section: Discussionmentioning

confidence: 99%

RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

Nicolazzo

Belardinilli

Vestri

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

Nicolazzo

Belardinilli

Vestri

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Liquid biopsy-guided genomic studies performed in colorectal cancer have demonstrated a significant increase in RAS mutant clones in plasma at the onset of secondary resistance to anti-EGFR therapy [ 11 ]. Similarly, the disappearance of RAS mutant clones in plasma has been demonstrated in a high percentage of patients who failed first-line treatments [ 12 ]. This frequent modulation of RAS mutations at the time of progressive disease had previously been described in leukemia patients as well [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments

et al. 2021

Self Cite

View full text Add to dashboard Cite

Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous advantages over tissue biopsies, tracking in real-time temporal-based tumor dynamics following each line of treatment. Here, we compared two liquid biopsy assays, specifically real-time polymerase chain reaction and next-generation sequencing, to track the KRAS G12C mutation at onset of progression from previous lines of therapy. The KRAS G12C mutation was acquired at the time of progressive disease in 24% of patients. Furthermore, all patients with KRAS G12C mutation-positive tissue became negative in ctDNA at progressive disease. The presence of other somatic mutations in all these samples confirmed the tumor origin of the circulating DNA. This pilot study suggests that in the assessment of the plasma KRAS G12C mutation as a druggable target, real-time PCR assay Idylla might be a suitable approach to better match patients to interventional biomarker-targeted therapies.

show abstract

“…Finally, the authors state that "studies with liquid biopsy have been to date selectively focused on the early detection of the appearance of RAS-mt clones in tumor deposits by analyzing ctDNA in blood samples from patients with RAS-wt primary tumors." This is also incorrect, and a comment on other studies currently ongoing on this specific topic 6 would have been appropriate and would have given greater substance to this interesting report.…”

mentioning

confidence: 96%

About RAS Mutation Clearance in Plasma ctDNA From RAS-Mutant Colorectal Cancer Patients

Gazzaniga

Nicolazzo

Caponnetto

et al. 2021

JCO Precision Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

Why the Therapeutic Impact of RAS Mutation Clearance in Plasma ctDNA Deserves to Be Further Explored in Metastatic Colorectal Cancer

Cited by 9 publications

References 18 publications

RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments

About RAS Mutation Clearance in Plasma ctDNA From RAS-Mutant Colorectal Cancer Patients

Contact Info

Product

Resources

About