{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:35:05Z","timestamp":1760240105483,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Newcastle Healthcare Charity","award":["JAG\/ML\/0614"],"award-info":[{"award-number":["JAG\/ML\/0614"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Dysfunctional homologous recombination DNA repair (HRR), frequently due to BRCA mutations, is a determinant of sensitivity to platinum chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi). In cultures of ovarian cancer cells, we have previously shown that HRR function, based upon RAD51 foci quantification, correlated with growth inhibition ex vivo induced by rucaparib (a PARPi) and 12-month survival following platinum chemotherapy. The aim of this study was to determine the feasibility of measuring HRR dysfunction (HRD) in other tumours, in order to estimate the frequency and hence wider potential of PARPi. A total of 24 cultures were established from ascites sampled from 27 patients with colorectal, upper gastrointestinal, pancreatic, hepatobiliary, breast, mesothelioma, and non-epithelial ovarian cancers; 8 were HRD. Cell growth following continuous exposure to 10 \u03bcM of rucaparib was lower in HRD cultures compared to HRR-competent (HRC) cultures. Overall survival in the 10 patients who received platinum-based therapy was marginally higher in the 3 with HRD ascites (median overall survival of 17 months, range 10 to 90) compared to the 7 patients with HRC ascites (nine months, range 1 to 55). HRR functional assessment in primary cultures, from several tumour types, revealed that a third are HRD, justifying the further exploration of PARPi therapy in a broader range of tumours.<\/jats:p>","DOI":"10.3390\/cancers11030354","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T04:15:29Z","timestamp":1552536929000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exploring the Frequency of Homologous Recombination DNA Repair Dysfunction in Multiple Cancer Types"],"prefix":"10.3390","volume":"11","author":[{"given":"Lucy","family":"Gentles","sequence":"first","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bojidar","family":"Goranov","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Northern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Matheson","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashleigh","family":"Herriott","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Northern Gynecological Oncology Centre, Queen Elizabeth Hospital, Sherriff Hill, Gateshead NE9 6SX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Hall","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Northern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asima","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Tata Medical Center, 14 MAR (E-W), New Town, Rajarhat, Kolkata 700 160, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6676-9224","authenticated-orcid":false,"given":"Yvette","family":"Drew","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Northern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola J.","family":"Curtin","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel L","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research, Paul O\u2019Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Northern Gynecological Oncology Centre, Queen Elizabeth Hospital, Sherriff Hill, Gateshead NE9 6SX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nrc3399","article-title":"DNA repair dysregulation from cancer driver to therapeutic target","volume":"12","author":"Curtin","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1200\/JCO.2008.16.0812","article-title":"A synthetic lethal therapeutic approach: Poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair","volume":"26","author":"Ashworth","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1056\/NEJMoa1105535","article-title":"Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer","volume":"366","author":"Ledermann","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S1470-2045(14)70228-1","article-title":"Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: A preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial","volume":"15","author":"Ledermann","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1470-2045(16)30559-9","article-title":"Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): An international, multicentre, open-label, phase 2 trial","volume":"18","author":"Swisher","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1056\/NEJMoa1611310","article-title":"Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer","volume":"375","author":"Mirza","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrc2342","article-title":"DNA repair pathways as targets for cancer therapy","volume":"8","author":"Helleday","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1158\/1078-0432.CCR-09-2758","article-title":"Development of a functional assay for homologous recombination status in primary cultures of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase inhibitors","volume":"16","author":"Mukhopadhyay","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2011). Integrated genomic analyses of ovarian carcinoma. Nature, 474, 609\u2013615.","DOI":"10.1038\/nature10166"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(17)32440-6","article-title":"Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"Coleman","year":"2017","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/bcr3670","article-title":"Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers","volume":"16","author":"Watkins","year":"2014","journal-title":"Breast Cancer Res. BCR"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.semradonc.2015.05.007","article-title":"DNA Damage Response Assessments in Human Tumor Samples Provide Functional Biomarkers of Radiosensitivity","volume":"25","author":"Willers","year":"2015","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gry, M., Rimini, R., Stromberg, S., Asplund, A., Ponten, F., Uhlen, M., and Nilsson, P. (2009). Correlations between RNA and protein expression profiles in 23 human cell lines. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-365"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1158\/0008-5472.CAN-12-0324","article-title":"Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: Sensitivity to PARP inhibitors, platinum, and survival","volume":"72","author":"Mukhopadhyay","year":"2012","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/bjc.2014.261","article-title":"Assessing the function of homologous recombination DNA repair in malignant pleural effusion (MPE) samples","volume":"111","author":"Patterson","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_16","unstructured":"(2019, March 08). PARP Inhibitor in Advanced Non-Small Cell Lung (PIN), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/results\/NCT01788332."},{"key":"ref_17","unstructured":"(2019, March 08). Trial of Gemcitabine\/Carboplatin with or without Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects with Previously Untreated Stage IV Squamous Non-Small Cell Lung (NSCLC) (ECLIPSE), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01082549."},{"key":"ref_18","unstructured":"(2019, March 08). Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients with Non-Small Cell Lung, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03308942."},{"key":"ref_19","unstructured":"(2019, March 08). A Study Evaluating the Efficacy and Tolerability of Veliparib in Combination with Paclitaxel\/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel\/Carboplatin Consolidation in Subjects with Stage III Non-Small Cell Lung, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02412371."},{"key":"ref_20","unstructured":"(2019, March 08). Study of Veliparib in Combination with Nivolumab and Platinum Doublet Chemotherapy in Participants with Metastatic or Advanced Non-Small Cell Lung (NSCLC), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02944396."},{"key":"ref_21","unstructured":"(2019, March 08). Randomized, Double-Blind, Multicenter, Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Advanced or Metastatic Squamous Non-Small Cell Lung, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02106546."},{"key":"ref_22","unstructured":"(2019, March 08). Veliparib with or without Radiation Therapy, Carboplatin, and Paclitaxel in Patients with Stage III Non-Small Cell Lung That Cannot Be Removed by Surgery, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01386385."},{"key":"ref_23","unstructured":"(2019, March 08). Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator\u2019s Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung (NSCLC) and Who Are Current or Former Smokers, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02264990."},{"key":"ref_24","unstructured":"(2019, March 08). Cisplatin and Etoposide with or without Veliparib in Treating Patients with Extensive Stage Small Cell Lung or Metastatic Large Cell Neuroendocrine Non-Small Cell Lung, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01642251."},{"key":"ref_25","unstructured":"(2019, March 08). Trial of CRLX101, a Nanoparticle Camptothecin With Olaparib in People with Relapsed\/Refractory Small Cell Lung, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02769962."},{"key":"ref_26","unstructured":"(2019, March 08). Olaparib Dose Escalating Trial + Concurrent RT With or Without Cisplatin in Locally Advanced NSCLC (olaparib), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01562210."},{"key":"ref_27","unstructured":"(2019, March 08). A Phase 2 Study of Cediranib in Combination with Olaparib in Advanced Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02498613."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1093\/annonc\/mdu384","article-title":"A phase II randomized study evaluating the addition of iniparib to gemcitabine plus cisplatin as first-line therapy for metastatic non-small-cell lung cancer","volume":"25","author":"Novello","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1158\/1078-0432.CCR-15-3069","article-title":"Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced\/Metastatic Non-Small Cell Lung Cancer","volume":"23","author":"Ramalingam","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1158\/1078-0432.CCR-10-2331","article-title":"Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib","volume":"17","author":"Kelly","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3322\/caac.21166","article-title":"Cancer statistics, 2013","volume":"63","author":"Siegel","year":"2013","journal-title":"CA Cancer J. Clin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0140-6736(10)62307-0","article-title":"Pancreatic cancer","volume":"378","author":"Vincent","year":"2011","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/gim.2017.85","article-title":"Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history","volume":"20","author":"Chaffee","year":"2018","journal-title":"Genet. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1158\/1055-9965.EPI-06-0783","article-title":"The prevalence of BRCA2 mutations in familial pancreatic cancer","volume":"16","author":"Couch","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/bjc.2016.41","article-title":"Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer","volume":"114","author":"Drew","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1038\/bjc.2014.91","article-title":"Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules","volume":"110","author":"Murray","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/jnci\/djq509","article-title":"Therapeutic Potential of Poly(ADP-ribose) Polymerase Inhibitor AG014699 in Human Cancers With Mutated or Methylated BRCA1 or BRCA2","volume":"103","author":"Drew","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s41467-017-00921-w","article-title":"Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes","volume":"8","author":"Riaz","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1073\/pnas.1013715108","article-title":"Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells","volume":"108","author":"Patel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","unstructured":"(2019, March 08). A Study of Niraparib Maintenance Treatment in Patients with Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02655016."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S1470-2045(11)70214-5","article-title":"Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: A phase 2, multicentre, open-label, non-randomised study","volume":"12","author":"Gelmon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/S1470-2045(16)30376-X","article-title":"Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: An updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial","volume":"17","author":"Ledermann","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_43","unstructured":"(2019, March 08). Maintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-Based Therapy, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03140670."},{"key":"ref_44","unstructured":"(2019, March 08). Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy (POLO), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02184195."},{"key":"ref_45","unstructured":"(2019, March 08). A Study of Rucaparib in Patients with Pancreatic Cancer and a Known Deleterious BRCA Mutation, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02042378."},{"key":"ref_46","unstructured":"(2019, March 08). Efficacy Study of Olaparib with Paclitaxel Versus Paclitaxel in Gastric Cancer Patients, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01063517."},{"key":"ref_47","unstructured":"(2019, March 08). Efficacy and Safety of Olaparib in Pretreated Patients with Measurable Colorectal Cancer, Stratified by Microsatellite Instability (MSI) Status, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00912743."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1093\/jnci\/djy085","article-title":"Biomarkers for Homologous Recombination Deficiency in Cancer","volume":"110","author":"Hoppe","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"O\u2019Donnell, R.L., McCormick, A., Mukhopadhyay, A., Woodhouse, L.C., Moat, M., Grundy, A., Dixon, M., Kaufman, A., and Soohoo Elattar, A. (2014). The use of ovarian cancer cells from patients undergoing surgery to generate primary cultures capable of undergoing functional analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090604"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1158\/2159-8290.CD-18-0474","article-title":"Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids","volume":"8","author":"Hill","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1097\/IGC.0000000000000745","article-title":"Advanced Ovarian Cancer Displays Functional Intratumor Heterogeneity That Correlates to Ex Vivo Drug Sensitivity","volume":"26","author":"Kaufmann","year":"2016","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa0900212","article-title":"Inhibition of poly(ADP-ribose) polymerase in tumours from BRCA mutation carriers","volume":"361","author":"Fong","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ejcsup.2007.09.002","article-title":"Progression-free survival as an end-point in clinical trials of biotherapeutic agents","volume":"5","author":"Bergmann","year":"2007","journal-title":"Eur. J. Cancer Suppl."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/3\/354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:26Z","timestamp":1760186306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/3\/354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,13]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["cancers11030354"],"URL":"https:\/\/doi.org\/10.3390\/cancers11030354","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2019,3,13]]}}}