2.

P- values for radiosensitisation by 11 drugs across a panel of 15 CRC cell lines

Cell line		LS411	Vaco5	RKO	HT29	OXCO4	CCK81	HCA7	DLD1	CW2	C10	HT55	C99	Colo678	SW403	SW1222
A panel of fifteen colorectal cell lines, selected for BRAF status in a heterogeneous mutational background, were treated with 11 drugs with or without 4 Gy radiation. Radiosensitisation shown is for the clinical radiosensitiser, 5-fluorouracil; two positive control drugs, SAHA and PI103; and compounds selected on the basis of primary screen P-values and potential clinical utility. Significance was determined by paired t-test on IC50 curve values following normalisation for radiation; ‘+’ indicates significant radiosensitisation, with the P-value indicated.
BRAF		BRAF V600E	BRAF V600E	BRAF V600E	BRAF V600E	BRAFV600E	BRAFWT	BRAFWT	BRAFWT	BRAFWT	BRAFWT	BRAFWT	BRAFWT	BRAFWT	BRAFWT	BRAFWT
MSI status		MSI	MSI	MSI	MSS	MSS	MSI	MSI	MSI	MSI	MSS	MSS	MSS	MSS	MSS	MSS
KRAS		KRAS WT	KRAS WT	KRAS WT	KRAS WT	KRAS WT	KRAS WT	KRAS WT	KRAS G13D	KRAS P140H	KRAS WT	KRAS WT	KRAS WT	KRAS G12D	KRAS G12V	KRAS A146V
EGFR		EGFR MUT	EGFR WT	EGFR WT	EGFR WT	Not known	EGFR Y1069C	EGFR WT	EGFR WT	EGFR G544*FS	EGFR WT	EGFR WT	EGFR WT	EGFR WT	EGFR WT	EGFR WT
Compound	Target	Radiosensitisation response (+ indicates significant radiosensitisation, with P value given below)
5-fluoro- uracil	Thymidylate synthase	ns	ns	ns	ns	ns	ns	ns	ns	+p≤0.01	ns	ns	ns	ns	ns	ns
SAHA	HDAC	ns	ns	+≤ 0.05	ns	+≤ 0.01	ns	ns	ns	ns	ns	+≤ 0.01	+≤ 0.05	+≤ 0.01	+≤ 0.01	+≤ 0.05
PI-103	PI3K/ DNAPK/ mTOR	+≤ 0.05	ns	+≤ 0.01	ns	+≤ 0.01	+≤ 0.05	+≤ 0.01	+≤ 0.01	+≤ 0.01	ns	ns	+≤ 0.01	+≤ 0.01	+≤ 0.05	+≤ 0.01
Olaparib	PARP	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	ns	ns	+≤ 0.01	+≤ 0.01	ns	+≤ 0.01	+≤ 0.01
Rucaparib	PARP	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.05	+≤ 0.01	+≤ 0.01	+≤ 0.01	ns	ns	+≤ 0.05	+≤ 0.05	ns	+≤ 0.01	+≤ 0.01
AZD-7762	CHK1 and 2	ns	ns	+≤ 0.05	ns	+≤ 0.01	+≤ 0.01	+≤ 0.05	+≤ 0.05	+≤ 0.01	+≤ 0.01	ns	+≤ 0.01	+≤ 0.01	+≤ 0.05	ns
PF477736	CHK1 and 2	+≤ 0.05	+≤ 0.05	+≤ 0.05	+≤ 0.05	+≤ 0.05	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.01	+≤ 0.05	ns	ns	+≤ 0.01	+≤ 0.05
AZD-6244	MEK1 and 2	ns	+≤ 0.05	+≤ 0.01	ns	+≤ 0.01	ns	+≤ 0.01	ns	+≤ 0.01	+≤ 0.05	+≤ 0.05	ns	+≤ 0.01	+≤ 0.01	+≤ 0.01
Trametinib	MEK1 and 2	+≤ 0.05	ns	+≤ 0.01	ns	ns	+≤ 0.05	+≤ 0.01	+≤ 0.01	ns	+≤ 0.05	ns	+≤ 0.05	+≤ 0.01	ns	+≤ 0.01
Mitoxantrone	TOPO II	ns	ns	ns	+≤ 0.05	ns	+≤ 0.05	+≤ 0.05	+≤ 0.01	+≤ 0.01	ns	+≤ 0.05	ns	ns	+≤ 0.01	ns
Vemurafenib	BRAF V600E	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns