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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]