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Table 2 Strategies to reverse resistance to anti-EGFR mAbs in preclinical studies

From: Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies

Therapy Target Agents Species Subpopulation Treatment regimen Efficiency Reference
New anti-EGFR mAbs EGFR ECD GC1118 PDXs KRAS mutation GC1118 VS cetuximab Sensitive VS insensitive [40]
MM-151 PDXs EGFR G465E MM-151 VS cetuximab/panitumumab Sensitive VS insensitive [41]
MEK inhibitor MEK Pimasertib Cell / Pimasertib + cetuximab Sensitive VS insensitive [42]
ERBB2 mABs ERBB2 4D5 Cell / 4D5+ cetuximab VS cetuximab Sensitive VS insensitive [43]
Trastuzumab Cell / Trastuzumab + cetuximab VS cetuximab Sensitive VS insensitive [44]
PI3K inhibitor PI3K BKM120 Cell/nude mice KRAS mutation Cetuximab + BKM120 VS cetuximab VS BKM120 More effective [45]
MET inhibitor MET Crizotinib Cell KRAS mutation Crizotinib VS cetuximab Sensitive VS insensitive [46]
Metabolic regulators AMPK Metformin Cell/ mice KRAS mutation Metformin+ cetuximab VS cetuximab Sensitive VS insensitive [47]
Metabolic regulators Methylglyoxal Carnosine Cell/mice KRAS mutation Carnosine + cetuximab VS cetuximab Sensitive VS insensitive [48]
Metabolic regulators BRAF Simvastatin Cell/mice KRAS mutation Simvastatin + cetuximab VS cetuximab mean tumor volume: 20.2vs 49.4cm3 [49]
Metabolic regulators Glutaminase 1 CB-839 Cell/mice KRAS WT CB-839 + cetuximab VS cetuximab Sensitive VS insensitive [50]
Metabolic regulators RAF L-ascorbic acid Cell/mice KRAS mutation L-ascorbic acid + cetuximab VS cetuximab Sensitive VS insensitive [51]
Immunity therapy NK cells anti-CD137 mAb Mice KRAS WT/mutaion anti-CD137 mAb + cetuximab Tumor regression and prolonged survival [52]
UCB-NK Cell EGFR (+) RAS mutation UCB-NK + cetuximab Sensitive VS insensitive [53]
Immunity therapy T cells BiTE Cell RAS and RAF mutation BiTE+ cetuximab vs cetuximab Sensitive VS insensitive [54]
Immunity therapy TLR9 IMO Cell KRAS mutation IMO + cetuximab VS cetuximab Sensitive VS insensitive [55, 56]
Immunity therapy CAFs Regorafenib Cell/ nude mice Unselected Regorafenib + cetuximab Sensitive VS insensitive [57]
BLU9931 Cell Unselected BLU9931 + cetuximab VS cetuximab Sensitive VS insensitive [58]
Cytotoxic drugs / TAS-102 PDXs / TAS-102+Panitumumab Response [59]
Natural bioactive monomer / β-elemene Cell / mice KRAS mutation β-elemene + cetuximab VS cetuximab Tumor growth inhibition and less lymph node metastasis [60]