Presence Of Amphiregulin Autocrine-loop Predicts Sensitivity Of EGFR Wild Type Cancers To Gefitinib And Cetuximab

Main Category: Cancer / Oncology
Article Date: 17 Apr 2008 - 4:00 PDT

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Researchers have discovered a biomarker in epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) cell lines. This so-called amphiregulin autocrine loop appears to predict response to the targeted therapies gefitinib and cetuximab.

"Amphiregulin expression could, in fact, be a suitable biomarker to select patients with EGFR wild-type NSCLC who would be likely to benefit from gefitinib or erlotinib," said lead researcher Kimio Yonesaka, M.D., Ph.D., a researcher at the Dana Farber Cancer Institute in Boston.

EGFR is a therapeutic target in both NSCLC and HNSCC. Patients with NSCLC who present with EGFR mutations are more likely to respond to gefitinib, according to the researchers. However, about 30 percent of patients treated with gefitinib or erlotinib maintain stable disease, defined as no tumor regression and no tumor growth, even without EGFR mutations.

"Most NSCLC patients that develop stable disease with gefitinib or erlotinib therapy do not harbor EGFR mutations," added co-researcher Pasi A. Jänne, M.D., Ph.D., Assistant professor of medicine at the Dana Farber Cancer Institute. "We have been interested in identifying biomarkers associated with stable disease as this is an important clinical benefit for non-small cell lung cancer patients."

The presence of amphiregulin varied significantly among the cell lines, ranging from 4.6 to 1,625.8 pg/mL, according to Yonesaka and colleagues. All four EGFR mutant cell lines from the NSCLC samples had negligible levels of amphiregulin. Of note, the researchers detected greater than 250 mg/mL of amphiregulin in seven of the 14 cell lines with wild-type EGFR. These NSCLC and HNSCC cell lines were sensitive to gefitinib and cetuximab. In contrast, cell lines producing less than 250 pg/mL of amphiregulin were resistant to both gefitinib and cetuximab.

Immunohistochemistry of tissue samples revealed that eight of the 10 samples of patients with stable disease following treatment with gefitinib had high amphiregulin expression the researchers report. Only one of 14 samples with high amphiregulin expression was from a patient with progressive disease (P < .001), suggesting that high amphiregulin expression was associated with the development of stable disease with gefitinib or erlotinib treatment, the researchers said.

Presence of amphiregulin autocrine-loop predicts sensitivity of EGFR wild type cancers to gefitinib and cetuximab
Abstract 4958

This was presented at the 2008 Annual Meeting of the American Association for Cancer Research.

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