Is the EGFR pathway relevant for the pathogenesis but not for treatment of acute myeloid leukemia?

Abstract

Despite intense research and the development of several new chemotherapeutics, the prognosis for specific subsets of acute myeloid leukemia (AML) has not improved significantly. Thus, the investigation of signaling pathways associated with the pathogenesis and progression of AML has become a source for the discovery of more effective treatments. The epidermal growth factor receptor (EGFR) belongs to the HER family of tyrosine kinase (TK) receptors and is involved in the progression of a variety of solid tumors. Although the expression of members of the HER family appears to be limited to epithelial tissues and derived neoplasms, there is evidence demonstrating their role in hematopoiesis and hematological neoplasms. In AML, preclinical studies and two anecdotal cases of response to EGFR TK inhibitors (TKI) supported the EGFR signaling pathway as a potential therapeutic target. Indeed, the presence of EGFR ligands in the bone marrow microenvironment has been shown to play pathological and regenerative/protective roles in AML. However, data reporting the expression of EGFR in AML remain controversial and the EGFR pathway inhibition in AML patients has demonstrated limited clinical significance. Further studies are required to determine the relevance of the EGFR pathway in AML biology and which patients may benefit from using EGFR TKI or other drugs that target TK receptors.

Keywords

Acute myeloid leukemia / epidermal growth factor receptor / EGFR ligands / EGFR tyrosine kinase inhibitors / gefitinib / erlotinib

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