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

Author(s)

de Almeida, Luciana Yamamoto ; Rego, Eduardo Magalhaes

• Document type: Journal article
• Source: JOURNAL OF CANCER METASTASIS AND TREATMENT; v. 7, p. 10-pg., 2021-01-01.

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. (AU)

• FAPESP's process: 16/02713-2 - Effects of erlotinib and gefitinib therapy in combination with all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: in vitro, ex vivo and murine experimental model studies.
• Grantee: Luciana Yamamoto de Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC