dc.contributor.author | Sheehan, B | |
dc.contributor.author | Neeb, A | |
dc.contributor.author | Buroni, L | |
dc.contributor.author | Paschalis, A | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Gil, V | |
dc.contributor.author | Miranda, S | |
dc.contributor.author | Crespo, M | |
dc.contributor.author | Guo, C | |
dc.contributor.author | Jiménez Vacas, J | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Ferreira, A | |
dc.contributor.author | Welti, J | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Sharp, A | |
dc.contributor.author | de Bono, J | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-07-19T10:20:39Z | |
dc.date.available | 2022-07-19T10:20:39Z | |
dc.date.issued | 2022-07-15 | |
dc.identifier | 698876 | |
dc.identifier.citation | Clinical Cancer Research, 2022, 28 (14), pp. 3104 - 3115 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5242 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-21-4531 | |
dc.description.abstract | PURPOSE: Prostate-specific membrane antigen (PSMA) targeting therapies such as Lutetium-177 (177Lu)-PSMA-617 are affecting outcomes from metastatic castration-resistant prostate cancer (mCRPC). However, a significant subset of patients have prostate cancer cells lacking PSMA expression, raising concerns about treatment resistance attributable at least in part to heterogeneous PSMA expression. We have previously demonstrated an association between high PSMA expression and DNA damage repair defects in mCRPC biopsies and therefore hypothesized that DNA damage upregulates PSMA expression. EXPERIMENTAL DESIGN: To test this relationship between PSMA and DNA damage we conducted a screen of 147 anticancer agents (NCI/NIH FDA-approved anticancer "Oncology Set") and treated tumor cells with repeated ionizing irradiation. RESULTS: The topoisomerase-2 inhibitors, daunorubicin and mitoxantrone, were identified from the screen to upregulate PSMA protein expression in castration-resistant LNCaP95 cells; this result was validated in vitro in LNCaP, LNCaP95, and 22Rv1 cell lines and in vivo using an mCRPC patient-derived xenograft model CP286 identified to have heterogeneous PSMA expression. As double-strand DNA break induction by topoisomerase-2 inhibitors upregulated PSMA, we next studied the impact of ionizing radiation on PSMA expression; this also upregulated PSMA protein expression in a dose-dependent fashion. CONCLUSIONS: The results presented herein are the first, to our knowledge, to demonstrate that PSMA is upregulated in response to double-strand DNA damage by anticancer treatment. These data support the study of rational combinations that maximize the antitumor activity of PSMA-targeted therapeutic strategies by upregulating PSMA. | |
dc.format | Print | |
dc.format.extent | 3104 - 3115 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Prostate-Specific Membrane Antigen Expression and Response to DNA Damaging Agents in Prostate Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-05-09 | |
dc.date.updated | 2022-07-19T10:20:00Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-21-4531 | |
rioxxterms.licenseref.startdate | 2022-05-12 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35552383 | |
pubs.issue | 14 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/20/21 Starting Cohort | |
pubs.publication-status | Published online | |
pubs.volume | 28 | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | PrCa Targeted Therapy | |
icr.researchteam | Translational Therapeutic | |
dc.contributor.icrauthor | Gurel, Bora | |
dc.contributor.icrauthor | Miranda, Susana | |
dc.contributor.icrauthor | Guo, Wei Yu | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | Sharp, Adam | |
dc.contributor.icrauthor | De Bono, Johann | |
icr.provenance | Deposited by Mr Arek Surman on 2022-07-19. Deposit type is initial. No. of files: 1. Files: 3104.pdf | |