Molecular Biomarkers in a Patient with Metastatic Colon Cancer Being Considered for Targeted Therapy with a Monoclonal Antibody to EGFR

Description

Antibodies directed against epidermal growth factor receptor (EGFR) on the cell surface of tumor cells can be effective in some patients with metastatic colon cancer. Testing for certain biomarkers can help to identify which patients may benefit and those who will not.

Monocloncal antibodies targeting EGFR:

(1) cetuximab

(2) panitumumab

Tests to perform:

(1) KRAS mutations

(2) BRAF mutations

(3) PIK3CA mutations

(4) PTEN protein expression by immunohistochemistry

Target	Name	Location	Function
KRAS	Kirsten rat sarcoma viral oncogene homolog	12p12.1	member of GTPase superfamily, mutated gene acts as oncogene
BRAF	v-raf murine sarcoma viral oncogene homolog B1	7q34	serine/threonine protein kinase, mutated gene acts as oncogene
PIK3CA	phosphatidylinositol-4,5- bisphosphate 3 kinase, catalytic subunit alpha	3q26.3	uses ATP to phosphorylate, mutated gene acts as oncogene
PTEN	phosphatase and tensin homolog	10q23.3	phosphatase that acts as a tumor suppressor

A patient who is wild-type to all of these targets has a good chance of responding to an anti-EGFR agent. However, not all of the resistance factors have been identified so the patient may not.

Finding	Effect
KRAS mutation	most are resistant to anti-EGFR therapy, mutation at codon 13 may show a clinical response
BRAF mutation at V600E	associated with worse progression free survival, may show some resistance to anti-EGFR therapy
PIK3CA mutation at exon 20	resistant to anti-EGFR therapy
low expression PTEN	lack of benefit from anti-EGFR therapy

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Description

Specialty

ICD-10