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Page 8 of 10 Almeida et al. J Cancer Metastasis Treat 2021;7:57 https://dx.doi.org/10.20517/2394-4722.2021.108

Despite the strong experimental evidence that EGFR inhibitors have an anti-leukemic activity in AML,
erlotinib and gefitinib have shown limited clinical efficacy. Erlotinib monotherapy failed to induce
[20]
[19]
differentiation and avoid disease progression in 26/29 (90%) patients with refractory or relapsed AML ,
while a response rate of 20% was achieved in azacytidine-resistant patients with AML/MDS
(myelodysplastic syndromes) . Moreover, the use of gefitinib as a single agent in a phase II trial conducted
[58]
in 18 patients with advanced AML did not promote an objective response, except for one patient who had
stable disease for 16 months . Similarly, in vitro treatment with gefitinib showed no difference in terms of
[18]
[8]
cytotoxic activity in leukemic blasts from patients with newly diagnosed or relapsed AML . Nevertheless,
these studies have potential limitations. Some hypotheses that could explain the failure of EGFR TKI
treatment in AML are the small number of patients, the lack of criteria for selection of patients expressing
EGFR or other biomarkers suitable for EGFR TKI therapy, an inadequate dose, and drug administration
only as monotherapy. Overall, the administration of gefitinib and erlotinib as single agents appears to be
well-tolerated, without significant organ/systemic toxicity [18-20,51,58] , encouraging further exploration of EGFR
TKI in combination with other drugs already used to treat AML in larger clinical trials.

CONCLUSION
EGFR signaling appears to support leukemogenesis or hematopoietic regeneration, depending on the cell
type and biological context in which the pathway is activated, but the complete characterization regarding
the expression and function of EGFR and other EGFR TKI responsive targets in the different compartments
of the leukemia microenvironment remains largely unknown. Therefore, the determination of predictive
biomarkers in the AML setting is necessary to guide which patients could benefit from selective targeted
TKI.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed bibliography review
and writing of the manuscript: de Almeida LY, Rego EM

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by FAPESP grant# 2013/08135-2 and FAPESP fellowship for de Almeida LY
(grant No. 2016/02713-2).

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2021.