Dataset Information

A PSMA-targeted theranostic approach is unlikely to be efficient in serous ovarian cancers.

ABSTRACT:

Purpose

Until now, results evaluating the expression of PSMA in ovarian cancer were sparse and contradictory. The aim was to reinvestigate the feasibility of a PSMA targeted theranostic approach in epithelial ovarian cancers with data from the tumour bank of a referring cancer centre.

Materials and methods

The OvaRessources Biological Resources Center database was screened from January 2004 to December 2017 to seek patients referred for the initial management of a serous epithelial ovarian cancer and for whom peritoneal histological samples were available in the tumour bank. Immunodetection of PSMA was performed to assess its cellular and neovascular expression. Slides were controlled by a certified pathologist, recorded as tiled tiff images and processed to compute the proportion of DAB stained surface.

Results

Of the 51 patients identified by the database screening, 32 patients were included resulting in 57 samples (32 pre-chemotherapy and 25 post-chemotherapy histological samples). Nine patients were chemo-sensitive, 10 were partially chemo-sensitive and 13 were chemo-resistant/refractory. In the entire dataset, the expression of PSMA was quasi-inexistent: %DAB_PSMA?=?0.04 (±?0.12) %. There was no significant difference in the %DAB_PSMA of sensitive, partially sensitive and resistant/refractory patients. There was also no significant difference in %DAB_PSMA in tumours before and after chemotherapy in the 25 patients for whom both samples were available.

Conclusion

The present work demonstrates that PSMA expression is negligible and a fortiori non-sufficient to ensure its usefulness as a prognosticator or a target for a theranostic strategy in ovarian cancers.

SUBMITTER: Aide N

PROVIDER: S-EPMC7873152 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

A PSMA-targeted theranostic approach is unlikely to be efficient in serous ovarian cancers.

Aide Nicolas N Poulain Laurent L Elie Nicolas N Briand Mélanie M Giffard Florence F Blanc-Fournier Cécile C Joly Florence F Lasnon Charline C

EJNMMI research 20210209 1

<h4>Purpose</h4>Until now, results evaluating the expression of PSMA in ovarian cancer were sparse and contradictory. The aim was to reinvestigate the feasibility of a PSMA targeted theranostic approach in epithelial ovarian cancers with data from the tumour bank of a referring cancer centre.<h4>Materials and methods</h4>The OvaRessources Biological Resources Center database was screened from January 2004 to December 2017 to seek patients referred for the initial management of a serous epithelia ...[more]

PMID: 33559764

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Project description:Cancer heterogeneity and drug resistance limit the efficacy of cancer therapy. To address this issue, we have developed an integrated treatment protocol for effective treatment of heterogeneous ovarian cancer. Methods: An amphiphilic polymer coated magnetic iron oxide nanoparticle was conjugated with near infrared dye labeled HER2 affibody and chemotherapy drug cisplatin. The effects of the theranostic nanoparticle on targeted drug delivery, therapeutic efficacy, non-invasive magnetic resonance image (MRI)-guided therapy, and optical imaging detection of therapy resistant tumors were examined in an orthotopic human ovarian cancer xenograft model with highly heterogeneous levels of HER2 expression. Results: We found that systemic delivery of HER2-targeted magnetic iron oxide nanoparticles carrying cisplatin significantly inhibited the growth of primary tumor and peritoneal and lung metastases in the ovarian cancer xenograft model in nude mice. Differential delivery of theranostic nanoparticles into individual tumors with heterogeneous levels of HER2 expression and various responses to therapy were detectable by MRI. We further found a stronger therapeutic response in metastatic tumors compared to primary tumors, likely due to a higher level of HER2 expression and a larger number of proliferating cells in metastatic tumor cells. Relatively long-time retention of iron oxide nanoparticles in tumor tissues allowed interrogating the relationship between nanoparticle drug delivery and the presence of resistant residual tumors by in vivo molecular imaging and histological analysis of the tumor tissues. Following therapy, most of the remaining tumors were small, primary tumors that had low levels of HER2 expression and nanoparticle drug accumulation, thereby explaining their lack of therapeutic response. However, a few residual tumors had HER2-expressing tumor cells and detectable nanoparticle drug delivery but failed to respond, suggesting additional intrinsic resistant mechanisms. Nanoparticle retention in the small residual tumors, nevertheless, produced optical signals for detection by spectroscopic imaging. Conclusion: The inability to completely excise peritoneal metastatic tumors by debulking surgery as well as resistance to chemotherapy are the major clinical challenges for ovarian cancer treatment. This targeted cancer therapy has the potential for the development of effective treatment for metastatic ovarian cancer.

Dataset Information

A PSMA-targeted theranostic approach is unlikely to be efficient in serous ovarian cancers.

Purpose

Materials and methods

Results

Conclusion

Publications

A PSMA-targeted theranostic approach is unlikely to be efficient in serous ovarian cancers.

Similar Datasets

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