Emerging RAS, BRAF, and EGFR mutations in cell-free DNA of metastatic colorectal patients are associated with both primary and secondary resistance to first-line anti-EGFR therapy.

Oncogenic RAS mutations are negative biomarkers of response to epidermal growth factor receptor (EGFR) blockade. RAS mutations are usually detected in biopsies of primary colorectal tumors. However, the genomic profiles of primary tumors and metastases are not always concordant, and chemotherapeutic agents can alter the tumor molecular landscape.

Cell-free DNA (cfDNA) is a novel tool to detect molecular heterogeneity. This study evaluated the clinical utility of cfDNA to predict primary or secondary resistance to EGFR blockade in patients with metastatic colorectal cancer. Thirty metastatic colorectal cancer patients without RAS and BRAF mutations were prospectively enrolled and treated with cytotoxic agents and EGFR blockade as first-line therapy. cfDNA was analyzed for the presence of RAS, BRAF, and EGFR (S492R) point mutations before initiating chemotherapy and every 2 months during chemotherapy.

Asprosin Magnetic Luminex Assay Kit

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Lumisterol (Lum) Magnetic Luminex Assay Kit

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Furin (FUR) Magnetic Luminex Assay Kit

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EUR 944.2

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Klotho (KL) Magnetic Luminex Assay Kit

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EUR 993.6

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Klotho (KL) Magnetic Luminex Assay Kit

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Leptin (LEP) Magnetic Luminex Assay Kit

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Leptin (LEP) Magnetic Luminex Assay Kit

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EUR 1043.1

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Leptin (LEP) Magnetic Luminex Assay Kit

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EUR 944.2

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EUR 1032.7

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EUR 1092.5

Leptin (LEP) Magnetic Luminex Assay Kit

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EUR 1117.8

Fusion (FUS) Magnetic Luminex Assay Kit

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Laminin (LN) Magnetic Luminex Assay Kit

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Gastrin (GT) Magnetic Luminex Assay Kit

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Gastrin (GT) Magnetic Luminex Assay Kit

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Ouabain (OB) Magnetic Luminex Assay Kit

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Midkine (MK) Magnetic Luminex Assay Kit

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Midkine (MK) Magnetic Luminex Assay Kit

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Noggin (NOG) Magnetic Luminex Assay Kit

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Oxytocin (OT) Magnetic Luminex Assay Kit

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Relaxin (RLN) Magnetic Luminex Assay Kit

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EUR 917.7

Relaxin (RLN) Magnetic Luminex Assay Kit

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EUR 1101.7

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Relaxin (RLN) Magnetic Luminex Assay Kit

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EUR 944.2

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Retinol (Ret) Magnetic Luminex Assay Kit

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EUR 1125.9

Glycine (Gly) Magnetic Luminex Assay Kit

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EUR 1200.6

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Lactase (LCT) Magnetic Luminex Assay Kit

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Visfatin (VF) Magnetic Luminex Assay Kit

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EUR 1159.2

Dopamine (DA) Magnetic Luminex Assay Kit

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EUR 1098.3

Fascin (FSCN) Magnetic Luminex Assay Kit

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Motilin (MTL) Magnetic Luminex Assay Kit

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Insulin (INS) Magnetic Luminex Assay Kit

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EUR 1043.1

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EUR 869.4

Insulin (INS) Magnetic Luminex Assay Kit

LKU603597-96T 96T
EUR 944.2

Insulin (INS) Magnetic Luminex Assay Kit

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EUR 1117.8

Insulin (INS) Magnetic Luminex Assay Kit

LKU603609-96T 96T
EUR 770.5

Insulin (INS) Magnetic Luminex Assay Kit

LKU603618-96T 96T
EUR 908.5

Insulin (INS) Magnetic Luminex Assay Kit

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EUR 944.2

Insulin (INS) Magnetic Luminex Assay Kit

LKU603638-96T 96T
EUR 1068.4

Ferritin (FE) Magnetic Luminex Assay Kit

LKU603782-96T 96T
EUR 770.5

Ferritin (FE) Magnetic Luminex Assay Kit

LKU603788-96T 96T
EUR 1043.1

Ferritin (FE) Magnetic Luminex Assay Kit

LKU603792-96T 96T
EUR 944.2

Ferritin (FE) Magnetic Luminex Assay Kit

LKU603809-96T 96T
EUR 894.7

Ferritin (FE) Magnetic Luminex Assay Kit

LKU603815-96T 96T
EUR 944.2

Decorin (DCN) Magnetic Luminex Assay Kit

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EUR 966

Trypsin (TRY) Magnetic Luminex Assay Kit

LKU606537-96T 96T
EUR 995.9

Trypsin (TRY) Magnetic Luminex Assay Kit

LKU606539-96T 96T
EUR 1043.1

Osterix (OSX) Magnetic Luminex Assay Kit

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EUR 1092.5

Osterix (OSX) Magnetic Luminex Assay Kit

LKU606895-96T 96T
EUR 1062.6

Latexin (LXN) Magnetic Luminex Assay Kit

LKU607102-96T 96T
EUR 993.6

Reelin (RELN) Magnetic Luminex Assay Kit

LKU607372-96T 96T
EUR 966

Reelin (RELN) Magnetic Luminex Assay Kit

LKU607374-96T 96T
EUR 993.6

Reelin (RELN) Magnetic Luminex Assay Kit

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EUR 1048.8

Tyrosol (Tyr) Magnetic Luminex Assay Kit

LKU607597-96T 96T
EUR 1186.8

Histamine (HA) Magnetic Luminex Assay Kit

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EUR 1098.3

Tafazzin (TAZ) Magnetic Luminex Assay Kit

LKU601431-96T 96T
EUR 966

Estradiol (E2) Magnetic Luminex Assay Kit

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Biglycan (BGN) Magnetic Luminex Assay Kit

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EUR 966

Biglycan (BGN) Magnetic Luminex Assay Kit

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Biglycan (BGN) Magnetic Luminex Assay Kit

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Vasorin (VASN) Magnetic Luminex Assay Kit

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EUR 966

Vasorin (VASN) Magnetic Luminex Assay Kit

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EUR 993.6

Paxillin (PXN) Magnetic Luminex Assay Kit

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EUR 944.2

Nephrin (NPHN) Magnetic Luminex Assay Kit

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EUR 869.4

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EUR 894.7

Nephrin (NPHN) Magnetic Luminex Assay Kit

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EUR 944.2

Secretin (SCT) Magnetic Luminex Assay Kit

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EUR 944.2

Secretin (SCT) Magnetic Luminex Assay Kit

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Bilirubin (Bb) Magnetic Luminex Assay Kit

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EUR 1125.9

E-selectin Magnetic Luminex Assay Kit

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EUR 1043.1

E-selectin Magnetic Luminex Assay Kit

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EUR 944.2

E-selectin Magnetic Luminex Assay Kit

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EUR 993.6

Ubiquitin (Ub) Magnetic Luminex Assay Kit

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EUR 938.4

Calnexin (CNX) Magnetic Luminex Assay Kit

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Cubilin (CUBN) Magnetic Luminex Assay Kit

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EUR 966

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Saitohin (STH) Magnetic Luminex Assay Kit

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Podocin (PDCN) Magnetic Luminex Assay Kit

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Podocin (PDCN) Magnetic Luminex Assay Kit

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EUR 944.2

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EUR 894.7

Glucagon (GCG) Magnetic Luminex Assay Kit

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EUR 770.5

Glucagon (GCG) Magnetic Luminex Assay Kit

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EUR 995.9

Glucagon (GCG) Magnetic Luminex Assay Kit

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EUR 944.2

The analysis was performed in 223 plasma samples from all 30 patients. Of the 30 patients, five had RAS mutations in their cfDNA before starting chemotherapy and did not respond. Twenty-four of the remaining 25 patients without cfDNA RAS mutations had a response. Twenty of the 24 responders developed secondary resistance and cfDNA RAS mutations were found in 17 of the 20. cfDNA BRAF mutations were found in seven, and EGFR mutations were found in eight of the 20 patients.

Emerging RAS, BRAF, and EGFR mutations occurred in patients with primary and secondary resistance to EGFR blockade. The detection of these mutations in cfDNA is a promising approach to predict treatment response and secondary resistance.