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Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs
OBJECTIVES: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. (131)I‐MIP‐1095 is a recently developed prostate‐specific membrane antigen (PSMA)‐targeting, small molecular weight radio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298040/ https://www.ncbi.nlm.nih.gov/pubmed/27139157 http://dx.doi.org/10.1111/jphp.12558 |
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author | Tesson, Mathias Rae, Colin Nixon, Colin Babich, John W. Mairs, Robert J. |
author_facet | Tesson, Mathias Rae, Colin Nixon, Colin Babich, John W. Mairs, Robert J. |
author_sort | Tesson, Mathias |
collection | PubMed |
description | OBJECTIVES: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. (131)I‐MIP‐1095 is a recently developed prostate‐specific membrane antigen (PSMA)‐targeting, small molecular weight radiopharmaceutical which has anti‐tumour activity as a single agent. Our purpose was to determine in vitro the potential benefit to be gained by combining (131)I‐MIP‐1095 with cytotoxic drug treatments. METHODS: Various cytotoxic agents were evaluated in combination with (131)I‐MIP‐1095 for their capacity to delay the growth of LNCaP cells cultured as multicellular tumour spheroids. Two end‐points were used to assess treatment efficacy: (i) the time required for doubling of spheroid volume and (ii) the area under the volume–time growth curves. KEY FINDINGS: The PARP‐1 inhibitor olaparib, the topoisomerase I inhibitor topotecan, the proteasome inhibitor bortezomib, the inhibitor of the P53–MDM2 interaction nutlin‐3 and the copper‐chelated form of the oxidising agent disulfiram (DSF:Cu) all significantly enhanced the inhibition of the growth of spheroids induced by (131)I‐MIP‐1095. However, the Chk1 inhibitor AZD7762 failed to potentiate the effect of (131)I‐MIP‐1095. CONCLUSIONS: These results indicate that targeted radiotherapy of prostate cancer may be optimised by combining its administration with chemotherapy. |
format | Online Article Text |
id | pubmed-5298040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-52980402017-02-22 Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs Tesson, Mathias Rae, Colin Nixon, Colin Babich, John W. Mairs, Robert J. J Pharm Pharmacol Molecular and Clinical Pharmacology OBJECTIVES: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. (131)I‐MIP‐1095 is a recently developed prostate‐specific membrane antigen (PSMA)‐targeting, small molecular weight radiopharmaceutical which has anti‐tumour activity as a single agent. Our purpose was to determine in vitro the potential benefit to be gained by combining (131)I‐MIP‐1095 with cytotoxic drug treatments. METHODS: Various cytotoxic agents were evaluated in combination with (131)I‐MIP‐1095 for their capacity to delay the growth of LNCaP cells cultured as multicellular tumour spheroids. Two end‐points were used to assess treatment efficacy: (i) the time required for doubling of spheroid volume and (ii) the area under the volume–time growth curves. KEY FINDINGS: The PARP‐1 inhibitor olaparib, the topoisomerase I inhibitor topotecan, the proteasome inhibitor bortezomib, the inhibitor of the P53–MDM2 interaction nutlin‐3 and the copper‐chelated form of the oxidising agent disulfiram (DSF:Cu) all significantly enhanced the inhibition of the growth of spheroids induced by (131)I‐MIP‐1095. However, the Chk1 inhibitor AZD7762 failed to potentiate the effect of (131)I‐MIP‐1095. CONCLUSIONS: These results indicate that targeted radiotherapy of prostate cancer may be optimised by combining its administration with chemotherapy. John Wiley and Sons Inc. 2016-05-03 2016-07 /pmc/articles/PMC5298040/ /pubmed/27139157 http://dx.doi.org/10.1111/jphp.12558 Text en © 2016 The Authors. Journal of Pharmacy and Pharmacology published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular and Clinical Pharmacology Tesson, Mathias Rae, Colin Nixon, Colin Babich, John W. Mairs, Robert J. Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs |
title | Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs |
title_full | Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs |
title_fullStr | Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs |
title_full_unstemmed | Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs |
title_short | Preliminary evaluation of prostate‐targeted radiotherapy using (131)I‐MIP‐1095 in combination with radiosensitising chemotherapeutic drugs |
title_sort | preliminary evaluation of prostate‐targeted radiotherapy using (131)i‐mip‐1095 in combination with radiosensitising chemotherapeutic drugs |
topic | Molecular and Clinical Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298040/ https://www.ncbi.nlm.nih.gov/pubmed/27139157 http://dx.doi.org/10.1111/jphp.12558 |
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