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

Santiago, B. García de; López-Gómez, Miriam; Delgado-López, Pedro David; Gordo, A. Jiménez; Neria, Fernando; Thuissard-Vasallo, I.J.; Gómez-Raposo, César; Tévar, Francisco Zambrana; Moreno-Rubio, Juan; Hernández, Alicia Martínez; Iglesias, I.; Casado, Enrique

doi:10.21873/invivo.12571

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…Similar to our study, Moati et al observed a 22.2% conversion rate of RAS mutant plasma samples to RAS wild type [25]. Several studies have noted the frequent occurrence of this conversion in metastatic colorectal cancer (mCRC), ranging from 8 to 70% [25][26][27][28][29]. There are various potential reasons for this phenomenon.…”

Section: Discussionsupporting

confidence: 89%

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

Zarkavelis,

Amylidi,

Torounidou

et al. 2024

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Section: Discussionsupporting

confidence: 89%

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

Zarkavelis,

Amylidi,

Torounidou

et al. 2024

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“…Similarly, Raimondi et al described the loss of RAS mutant clones in plasma of mCRC patients, all treated with anti-VEGF [4]. More recently, Garcia de Santiago et al showed that the RAS mutation status had changed to wild-type * in 73.9% of originally RAS mutant mCRC treated with antiangiogenics [23]. Conversely, Klein-Scory et al reported that in patients with initially RAS mutated mCRC, RAS mutations rapidly disappeared in liquid biopsy during first-line therapy, independent of type of chemotherapy and irrespective of anti-VEGF treatments [5].…”

Section: Discussionmentioning

confidence: 95%

“…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

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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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“…Half of the patients analyzed by Gazzaniga et al [26] changed their mutational status to become RAS wild-type after receiving antiangiogenic therapy. Garcia et al [27] detected a RAS mutational change in 74% of patients after a median of 3 months of bevacizumab treatment. Even traditional chemotherapy has been linked to the modification of the RAS mutational status.…”

Section: Of 11mentioning

confidence: 99%

Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

Sayagués,

Montero,

Jiménez-Pérez

et al. 2023

IJMS

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Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circulating tumor DNA (ctDNA) and tumoral tissue DNA (ttDNA) from 51 synchronous metastatic colorectal carcinoma (SMCC) patients by real-time PCR, and their relationship with the clinical, biological and histological features of disease at diagnosis. The highest frequency of mutations detected was in the KRAS gene, in tumor biopsies and plasma samples, followed by mutations of the PIK3CA, NRAS and BRAF genes. Overall, plasma systematically contained those genetic abnormalities observed in the tumor biopsy sample from the same subject, the largest discrepancies detected between the tumor biopsy and plasma from the same patient being for mutations in the KRAS and PIK3CA genes, with concordances of genotyping results between ttDNA and ctDNA at diagnosis of 75% and 84%, respectively. Of the 51 SMCC patients in the study, 25 (49%) showed mutations in at least 1 of the 4 genes analyzed in patient plasma. From the prognostic point of view, the presence and number of the most common mutations in the RAS, PIK3CA and BRAF genes in plasma from SMCC patients are independent prognostic factors for OS. Determination of the mutational status of ctDNA in SMCC could be a key tool for the clinical management of patients.

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

Cited by 5 publications

References 16 publications

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

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

Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

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