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Page 6 of 10                                                                       Almeida et al. J Cancer Metastasis Treat 2021;7:57  https://dx.doi.org/10.20517/2394-4722.2021.108


                             Table 1. Effects of EGFR inhibitors in AML

                              Study                Sample                                            Study design                   Type of EGFR inhibitor       Result
                                         [2]
                              Boehrer et al. , 2008  P39, KG-1, HL-60 EGFR negative AML cell lines   In vitro and in vivo treatments   Erlotinib                 Off-target effects: differentiation, cell cycle arrest, and
                                                        +
                                                   CD34  EGFR negative AML primary blasts                                                                        apoptosis
                                                   SCID mice inoculated with KG-1 cells                                                                          Apoptosis
                                                                                                                                                                 Reduced tumor growth
                                     [5]
                              Sun et al. , 2012    HL-60, HEL, Molt-4, and Hut78 EGFR negative AML cell   In vitro treatment        Cetuximab (monoclonal antibody  EGFR positive AML cells are responsive to the
                                                   lines                                                                            anti-EGFR)                   cytotoxicity of cetuximab
                                                   K562 and CEM EGFR positive AML cell lines
                                                   EGFR negative and positive AML primary cells
                                           [6]
                              Stegmaier et al. ,   HL-60, Kasumi-1, U937 EGFR negative AML cell lines   In vitro treatment          Gefitinib                    Off-target effects: cell differentiation
                              2005                 AML primary blasts                                                                                            Cell viability inhibition and differentiation
                                         [7]
                              Boehrer et al. , 2008   P39, MOLM-13, MV4-11, U937, HL-60, KG-1 MDS    In vitro treatment             Erlotinib and gefitinib      Off-target effects: cell viability inhibition, differentiation,
                                                   (myelodysplastic syndrome)/AML cell lines                                                                     and apoptosis
                                                        +
                                                   CD34  EGFR negative MDS/AML primary blasts
                                           [8]
                              Lindhagen et al. ,   AML primary blasts and MV4-11 EGFR negative AML cell  In vitro treatment with gefitinib   Gefitinib alone or combined to   Off-target effects: apoptosis via caspase-3 pathway
                              2008                 lines                                             alone or combined to standard   standard antileukemic drugs  Synergistic interaction with etoposide
                                                                                                     antileukemic drugs                                          Additive interactions with doxorubicin, cytarabine, and
                                                                                                                                                                 cisplatin
                                         [13]
                              Miranda et al.  , 2008  HL-60, NB4, U937 AML cell lines                In vitro treatment             Gefitinib alone or combined to   Gefitinib enhanced ATRA-induced cell differentiation
                                                                                                                                    all-trans retinoic acid (ATRA)  MEK/ERK pathway is potentially involved in the process
                                                                                                                                                                 of AML differentiation induced by ATRA/gefitinib
                                     [14]
                              Noh et al.  , 2010   NB4 AML cell line                                 In vitro treatment             Gefitinib and arsenic trioxide   Gefitinib enhanced ATO-induced cell differentiation and
                                                                                                                                    (ATO)                        reactive oxygen species (ROS) generation
                                                                                                                                                                 ERK pathway is required for gefitinib enhancement of
                                                                                                                                                                 ATO-induced cell differentiation
                                                                                                                                                                 P38 MAPK pathway is potentially involved in the process
                                                                                                                                                                 of AML differentiation induced by ATO/gefitinib
                                      [15]
                              Hahn et al.  , 2009   HL-60 AML cell line                              Mass spectrometry and RNAi     Gefitinib                    Syk was identified as a target for gefitinib-induced cell
                                                                                                     screening                                                   differentiation
                                                                                                                                                                 Gefitinib inhibits Syk phosphorylation
                                     [16]
                              Cao et al.  , 2020   MV4-11 and KG-1 AML cell lines                    In vitro and in vivo treatments   Erlotinib                 Erlotinib inhibits the in vitro growth of MV4-11 and KG-1
                                                                                                                                                                 cells via targeting FLT3 and Lyn, respectively
                                                                                                                                                                 Erlotinib inhibits the in vivo growth of MV4-11 cells
                                         [17]
                              Boehrer et al.  , 2011    KG-1, KG-1a, MOLM-13, and HL-60 AML cell lines   In vitro treatment         Erlotinib alone or combined to   Synergistic interaction in reducing the proliferation of
                                                                                                                                    rapamycin                    AML cells by decreasing the constitutive activation of
                                                                                                                                                                 SRC family kinases (SFK)
                                          [18]
                              Deangelo et al.  , 2014  18 (11 relapsed) AML patients negative for FLT3-ITD   Phase II prospective non-  Gefitinib                No patients had objective responses
                                                   mutation with a median age of 72 (range 57-84 years)  randomized clinical trial                               1 patient had a prolonged stable disease (16 months)
                                           [19]
                              Abou Dalle et al.  ,   29 relapsed/refractory AML patients with a median age   Pilot phase II prospective non-  Erlotinib          26 patients (90%) discontinued therapy due to disease
                              2018                 of 67 (range 20-83 years)                         randomized clinical trial                                   progression
                                                                                                                                                                 2 patients discontinued therapy due to adverse events
                                                                                                                                                                 2 patients had > 50% reduction in bone marrow blasts
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