REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
EGFR, Rabbit monoclonal	Cell Signaling Technology	Cat#4267; RRID:AB_2246311
pEGFR (Y1068), Rabbit polyclonal	Cell Signaling Technology	Cat#2234; RRID:AB_331701
HER2, Rabbit monoclonal	Cell Signaling Technology	Cat#4290; RRID:AB_10557104
pHER2 (Y1221/1222), Rabbit polyclonal	Cell Signaling Technology	Cat#2249; RRID:AB_2099241
HER3, Rabbit monoclonal	Cell Signaling Technology	Cat#12708; RRID:AB_2721919
pHER3(Y1289), Rabbit monoclonal	Cell Signaling Technology	Cat#4791; RRID:AB_2099709
IGF1Rβ, Rabbit monoclonal	Cell Signaling Technology	Cat#9750; RRID:AB_10950969
AXL, Rabbit monoclonal	Cell Signaling Technology	Cat#8661; RRID:AB_11217435
MET, Rabbit monoclonal	Cell Signaling Technology	Cat#8198; RRID:AB_10858224
ERK1/2, Rabbit monoclonal	Cell Signaling Technology	Cat#4695; RRID:AB_390779
pERK1/2 (Y202/204), Rabbit polyclonal	Cell Signaling Technology	Cat#9101; RRID:AB_331646
AKT1, Rabbit monoclonal	Cell Signaling Technology	Cat#2938; RRID:AB_915788
pAKT (S473), Rabbit monoclonal	Cell Signaling Technology	Cat#4060; RRID:AB_2315049
Caspase 3, Rabbit polyclonal	Cell Signaling Technology	Cat#9662; RRID:AB_331439
Cleaved Caspase 3 (D175), Rabbit polyclonal	Cell Signaling Technology	Cat#9661; RRID:AB_2341188
BIM, Rabbit monoclonal	Cell Signaling Technology	Cat#2933; RRID:AB_1030947
Survivin, Rabbit polyclonal	Cell Signaling Technology	Cat#2803; RRID:AB_490807
p27, Rabbit monoclonal	Cell Signaling Technology	Cat#3686; RRID:AB_2077850
γH2AX (S139), Rabbit	Cell Signaling Technology	Cat#2577; RRID:AB_2118010
AURKA, Rabbit monoclonal	Cell Signaling Technology	Cat#4718; RRID:AB_2061482
FOXM1, Rabbit monoclonal	Cell Signaling Technology	Cat#5436; RRID:AB_10692483
Cyclin B1, Rabbit monoclonal	Cell Signaling Technology	Cat#12231; RRID:AB_2783553
RAD18, Rabbit monoclonal	Cell Signaling Technology	Cat#9040; RRID:AB_2756446
GAS6, Rabbit monoclonal	Cell Signaling Technology	Cat#67202; RRID:AB_2799720
RAD51, Rabbit monoclonal	Cell Signaling Technology	Cat#8875; RRID:AB_2721109
Ub1-PCNA (K164), Rabbit monoclonal	Cell Signaling Technology	Cat#13439; RRID:AB_2798219
PCNA, Mouse monoclonal	Cell Signaling Technology	Cat#2586; RRID:AB_2160343
FOXO3A, Rabbit monoclonal	Cell Signaling Technology	Cat#2497; RRID:AB_836876
KI67, Mouse monoclonal	Cell Signaling Technology	Cat#9449; RRID:AB_2797703
β-Actin, Rabbit polyclonal	Cell Signaling Technology	Cat#4967; RRID:AB_330288
GAPDH, Mouse monoclonal	Millipore	Cat#MAB374; RRID:AB_2107445
Vinculin, Mouse monoclonal	Sigma-Aldrich	Cat#V9264; RRID:AB_10603627
Pol η, Rabbit polyclonal	Abcam	Cat#ab234855
Pol κ, Rabbit polyclonal	Abcam	Cat#ab86076; RRID:AB_1925334
MLH1, Rabbit monoclonal	Abcam	Cat#ab92312; RRID:AB_2049968
MSH2, Rabbit monoclonal	Abcam	Cat#ab92473; RRID:AB_10585291
KIF4A, Rabbit polyclonal	Aviva Systems Biology	Cat#OAGA05174; RRID:AB_2861368
BRCA1, Rabbit polyclonal	Santa Cruz Biotechnology	Cat#sc-642; RRID:AB_630944
Anti-mouse Alexa Fluor 555-conjugated secondary antibody	Thermo Fisher Scientific	Cat#A-31570; RRID:AB_2536180
Anti-rabbit Alexa Fluor 555-conjugated secondary antibody	Thermo Fisher Scientific	Cat#A-31572; RRID:AB_162543
Biological samples
Patient derived xenograft (PDX) TM00199	The Jackson Laboratory	TM00199
Patient derived xenograft (PDX) TM00193	The Jackson Laboratory	TM00193
Patient derived xenograft (PDX) TM00253	The Jackson Laboratory	TM00253
Chemicals, peptides, and recombinant proteins
Erlotinib	LC Laboratories	Cat#E−4997
Osimertinib	Gift from Astrazeneca	N/A
Cetuximab (Erbitux®)	Merck	N/A
Trastuzumab (Herceptin®)	Roche	N/A
Panitumumab (Vectibix®)	Amgen	N/A
mAb565	Generated in our lab19	N/A
mAb111	Generated in our lab19	N/A
NAC (N-acetyl-L-cysteine)	Sigma-Aldrich	Cat# A9165; CAS: 616-91-1
DHE (Dihydroethidium)	Thermo Fisher Scientific	Cat# D11347
DCFDA (2ʹ,7ʹ-Dichlorofluorescin Diacetate)	Thermo Fisher Scientific	Cat#D399
Triton X-100	Sigma-Aldrich	Cat#T8787; CAS: 9036-19-5
MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)	Sigma-Aldrich	Cat#M5655; CAS: 298-93-1
FITC-labeled phalloidin	Sigma-Aldrich	Cat#P5282
Critical commercial assays
FuGENE HD Transfection Reagent	Promega	Cat#E2311
Experimental models: Cell lines
H3255	National Cancer Institute (NCI)	RRID:CVCL_6831
11–18	Riken BRC	RRID:CVCL_6659
PC9	Gift from Julian Downward, Francis Crick Institute, London	RRID:CVCL_B260
PC9ER	Gift from Julian Downward, Francis Crick Institute, London	N/A
HCC4006	ATCC	Cat# CRL-2871; RRID:CVCL_1269
HCC2935	ATCC	Cat# CRL-2869; RRID:CVCL_1265
HCC827	Gift from Ravid Straussman, Weizmann Institute of Science, Israel	RRID:CVCL_2063
H1975	ATCC	Cat# CRL-5908; RRID:CVCL_1511
HEK293T	ATCC	Cat# CRL-3216; RRID:CVCL_0063
Experimental models: Organisms/strains
CD1 nude mice (HsdHli:CD1-Foxn1nu)	Envigo Israel	N/A
NSG mice	The Jackson Laboratory	RRID:IMSR_JAX:005557
Recombinant DNA
Fucci(CA)2/pCSII-EF	RIKEN BRC	RDB15446
psPAX2	Addgene	Plasmid #12260
pMD2.G	Addgene	Plasmid #12259
Software and algorithms
GraphPad Prism v8.0.2	GraphPad Software	RRID:SCR_002798
ImageJ v1.53t	National Institute of Health (NIH)	RRID:SCR_003070
Cell Profiler v4.2.1	Broad Institute	RRID:SCR_007358
Image Lab v6.0.1	Bio-Rad	RRID:SCR_014210
ReViSP v2.3	Piccinini et al.60 Piccinini et al.61	N/A
IncuCyte S3 software	Sartorius	RRID:SCR_023147
R v4.2.1	The R Foundation	RRID:SCR_001905