Enhancing the anti-tumour activity of 177Lu-DOTA-octreotate radionuclide therapy in somatostatin receptor-2 expressing tumour models by targeting PARP.
Sci Rep
; 10(1): 10196, 2020 06 23.
Article
en En
| MEDLINE
| ID: mdl-32576907
ABSTRACT
Peptide receptor radionuclide therapy (PRRT) is an important treatment option for patients with somatostatin receptor-2 (SSTR2)-expressing neuroendocrine tumour (NET) though tumour regression occurs in only a minority of patients. Therefore, novel PRRT regimens with improved therapeutic activity are needed. Radiation induced DNA damage repair is an attractive therapeutic target to increase PRRT efficacy and consequently, we have characterised a panel of preclinical models for their SSTR2 expression, in vivo growth properties and response to 177Lu-DOTA-octreotate (LuTate) PRRT to identify models with features suitable for evaluating novel therapeutic combinations. In vitro studies using the SSTR2 expressing AR42J model demonstrate that the combination of LuTate and the small molecule Poly(ADP-ribose) polymerase-1 (PARP) inhibitor, talazoparib led to increased DNA double strand breaks, as assessed by γ-H2AX foci formation, as compared to LuTate alone. Furthermore, using the AR42J tumour model in vivo we demonstrate that the combination of LuTate and talazoparib significantly improved the anti-tumour efficacy of LuTate alone. These findings support the clinical evaluation of the combination of LuTate and PARP inhibition in SSTR2-expressing NET.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos Organometálicos
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Octreótido
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Poli(ADP-Ribosa) Polimerasas
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Receptores de Somatostatina
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Tumores Neuroendocrinos
/
Lutecio
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia