Supplementary Figure S1: Distribution of LC50 values for (a) Carboplatin, (b) Doxorubicin, (c) Gemcitabine, (d) Topotecan, (e) Paclitaxel, and (f) Rucaparib, across the cell line panel. The dotted line represents the median LC50 value. Each data point represents Mean ± SD LC50 for that cell line.

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Supplementary Figure 2: Distribution of survival % at given concentration of (a) Carboplatin, (b) Doxorubicin, (c) Gemcitabine, (d) Topotecan, (e) Paclitaxel, and (f) Rucaparib, across the cell line panel. The dotted line represents the median survival % value of the cell lines. Each data represents Mean ± SEM of the survival % of 3 independent experiments for that cell line.

Supplementary Figure S3: Hierarchical clustering of % Survival at fixed drug concentration for each of the14 cell lines in the panel.

Supplementary Figure S4: Correlation between in-house RNA-Seq data and published data on 9 ovarian cancer cell lines to confirm the identity of the cell lines. Pearson’s correlation coefficients and the corresponding p-values between the two datasets for 2495 genes used to generate the volcano plot shows a positive correlation for most genes. The average Pearson’s correlation coefficient across all genes was 0.58. [The red line indicates p-value of 0.05 and the blue line indicates an r-value of 0.5].

Supplementary Figure S5: Hierarchical clustering of Pearson’s correlation co-efficient of normalized gene expression values and % survival at a fixed concentration of drug (Carboplatin: 10 µM; Doxorubicin: 100 nM; Gemcitabine: 30 nM; Topotecan: 30 nM; Paclitaxel: 30 nM and Rucaparib: 10 µM)

Supplementary Figure S6: Growth inhibition analysis of the patient ascites-derived primary cultures following treatment with carboplatin, rucaparib, doxorubicin, gemcitabine, topotecan and paclitaxel. Dotted line represents the concentration corresponding to the GI50 value for each sample and the corresponding drug. The samples are classified into HRR competent (HRC, red lines) and HRR defective (HRD, blue lines) identified using functional γH2AX-RAD51 foci formation assay (data not shown).

Supplementary Figure S7: Correlation of functional activity of (A) NHEJ pathway and (B) intrinsic oxidative stress with sensitivity to the different drugs

Table S1: Culture media used for the maintenance of the cell lines

Cell Line Original Ranking as Morphology Tumour Source Pre-culture clinical treatment status Culture Media Doubling Histopathological HGSOC/non- Time (Hrs) Classification HGSOC

Kuramochi Undifferentiated HGSOC Epithelial Peritoneal ascites Unknown RPMI 1640, 40 adenocarcinoma 10% FBS COV318 HGS HGSOC Epithelial Peritoneal ascites Unknown DMEM, 10% 67 FBS CAOV3 Adenocarcinoma HGSOC Epithelial Ovarian solid Unknown DMEM, 10% 73 tumour FBS

ES2 Clear Cell HGSOC Spindle Ovarian solid Unknown [The cells exhibit low to moderate RPMI 1640, 21 tumour resistance to a number of chemotherapeutic agents 10% FBS including doxorubicin, cisplatin, carmustine, etoposide and cyanomorpholinodoxorubicin (MRA-CN)] OAW42 Cystadenocarcinoma Non-HGSOC Epithelial Peritoneal ascites At passage 4 the cell line showed resistance to RPMI 1640, 49 doxorubicin [adriamycin (ADM)], phosphoramide 10% FBS mustard (PM), and cisplatin [cis- dichlorodiammineplatinum(II)] (CIS) but rapidly reverted to CIS sensitivity. At passage 25 the cell line was still resistant to ADM and PM (Wilson et al, 1984) A2780 Adenocarcinoma Non-HGSOC Round Ovarian solid Untreated RPMI 1640, 10 21 tumour % FBS CP70-B1 N/A Non-HGSOC Round Derivative of CP70 Derivative of CP70 which are derivatives of A2780 RPMI 1640, 10 27 which are % FBS + 200 derivatives of A2780 µg/ml Hygromycin B CP70-A2 N/A Non-HGSOC Round Derivative of CP70 Derivative of CP70 which are derivatives of A2780 RPMI 1640, 10 20 which are % FBS + 200 derivatives of A2780 µg/ml Hygromycin B IGROV1 Mixed endometrioid, Non-HGSOC Epithelial Ovarian solid Untreated RPMI 1640, 10 33 serous, cell cell, tumour % FBS undifferentiated UWB1.289+BRCA1 HGS HGSOC Epithelial Recurrent Ovarian Treated 50% RPMI- 51 Cancer (earlier 1640 + 50% Breast Cancer) MEGM Bullet Kit medium + 200 µg/ml G- 418 NUCOLL43 Clear Cell Non-HGSOC Epithelial Peritoneal acsites Untreated RPMI 1640, 20 54 % FBS NIH-OVCAR3 Adenocarcinoma HGSOC Epithelial Peritoneal acsites Combination chemotherapy with RPMI 1640, 10 53 Cyclophosphamide, Adriamycin, and cisplatin % FBS UWB1.289 Serous Non-HGSOC Epithelial Recurrent Ovarian Treated 50% RPMI- 52 Cancer (earlier 1640 + 50% Breast Cancer) MEGM Bullet Kit medium COV362 Endometriod HGSOC Spindle Pleural effusion Unknown DMEM, 10% 73 FBS HGSOC: High Grade Serous Ovarian Cancer; FBS: Fetal Bovine Serum Table S2: Cell line panel mutation or amplification status of frequent genomic alterations reported in High Grade Serous Ovarian Cancers (cbioportal)

Cell line TP53 BRCA BRCA CCNE RB1 MMR MYC ARID EMS 1 2 1 1A Y Kuramochi Mut Mut Amp COV318 Mut Low Amp Exp CAOV3 Mut Amp Low Exp ES2 Mut

OAW42 WT Mut High Amp Mut Exp A2780 WT High Comp Mut Exp CP70-B1 Mut Comp CP70-A2 Mut Def IGROV1 Mut Mut Mut Mut UWB1.289+BRCA1 Mut WT NUCOLL43 Null NIH-OVCAR3 Mut Amp Amp UWB1.289 Mut Mut COV36 Mut Mut Low Amp Amp Exp Mut: Mutated; WT: Wild-type; Amp: Amplification; Low Exp: Low mRNA Expression; High Exp: High mRNA expression; Comp: Competent; Def: Defective

Table S3: Correlation between % Survival at fixed drug concentration and Area Under the Curve (AUC) of the survival curves of the 14 cell lines for each drug

Carboplatin Doxorubicin Gemcitabine Topotecan Paclitaxel Rucaparib Pearson’s 0.992393 0.95823 0.858857 0.763185 0.951332 0.993379 Correlation coefficient p-val <0.0001 <0.0001 <0.0001 0.0015 <0.0001 <0.0001

Table S4: Homologous Recombination Repair defect (BRCA mutation and functional HRR status) and the chemosensitivity to six chemotherapy drugs for the patient ascites-derived primary cultures

Sample List BRCA HRR Carbopl Rucapa Doxorub Gemcita Paclita Topote status Status atin rib icin GI50 bine xel can GI50 GI50 (nM) GI50 GI50 GI50 (µM) (µM) (nM) (nM) (nM) NEOCATS- gBRCA HRD 2.4 4 97.6 24.4 2.1 23.5 A-003 wildtype NEOCATS- gBRCA HRC 10.5 >30 27.6 44.6 6.2 17.4 A-005 wildtype NEOCATS- gBRCA HRD 2.5 4 55.6 60.6 2.5 24.1 A-014 wildtype NEOCATS- Unknow HRD 10.6 14 23.5 26.5 6.2 19.2 A-017 n NEOCATS- gBRCA HRC 7.7 >30 10 14.2 2.7 4.1 A-018 wildtype NEOCATS- Unknow HRD 4.9 0.56 14.7 5.6 2.5 28.5 A-022 n NEOCATS- gBRCA1 HRC 2.1 7 21.3 57.1 2.2 47.5 A-023 mutant NEOCATS- gBRCA HRC 5.4 7.8 44.2 71.3 5.6 25.3 A-026 wildtype NEOCATS- Unknow HRC 10.6 11.7 48.7 75.2 4.1 101.7 A-029 n NEOCATS- somatic HRD 2.1 14.8 28.1 119.6 9.9 82.1 A-030 BRCA mutant

Table S5: Pearson’s correlation analysis between %NHEJ activity and % survival at given concentrations of the drugs

Drug Correlation coefficient Outliers (ES2 and OAW42) removed Carboplatin 10 µM -0.31 -0.31

Doxorubicin 100 nM 0.11 0.46 Gemcitabine 30 nM 0.36 0.5 Topotecan 30 nM 0.08 0.02 Paclitaxel 30 nM 0.4 0.34 Rucaparib 10 µM -0.35 -0.32

Table S6: Pearson’s correlation analysis between Baseline 8-OHdG levels and % survival at given concentrations of the drugs

Drug Correlation co-efficient Carboplatin 10 µM 0.21 Doxorubicin 100 nM 0.34 Gemcitabine 30 nM -0.4 Topotecan 30 nM 0.05 Paclitaxel 30 nM 0.2 Rucaparib 10 µM 0.23