Preclinical evaluation of the antitumor activity of a new CXCR4 inhibitor: a novel therapeutic approach in diffuse large B-cell lymphoma
Constitutive activation of the chemokine receptor CXCR4 is associated with tumor progression, invasion and resistance to treatment. Overexpression of CXCR4 in diffuse large B-cell lymphoma (DLBCL) confers a reduced prognosis. However, the biological relevance of this receptor in DLBCL progression re...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/663897 |
| Acceso en línea: | http://hdl.handle.net/10803/663897 |
| Access Level: | acceso abierto |
| Palabra clave: | Oncologia Oncología Oncology Hematologia Hematología Hematology Limfomes Linfomas Lymphomas Desenvolupament de medicaments Desarrollo de los medicamentos Drug development Ciències de la Salut 616 |
| Sumario: | Constitutive activation of the chemokine receptor CXCR4 is associated with tumor progression, invasion and resistance to treatment. Overexpression of CXCR4 in diffuse large B-cell lymphoma (DLBCL) confers a reduced prognosis. However, the biological relevance of this receptor in DLBCL progression remains underexplored. In this thesis, the new CXCR4 inhibitor IQS-01.01 has been preclinicaly evaluated in in vitro and in vivo models of DLBCL. It has been concluded that 1) inhibition of CXCR4 presents antitumor properties in DLBCL, 2) that IQS-01.01RS holds better pharmacological properties than the reference CXCR4 inhibitor, AMD3100 3) that treatment with IQS- 01.01RS reduces the levels of the oncogene MYC and 4) that the combinantion of IQS- 01.01RS with the BET-bromodomain inhibitor, CPI203, is synergistic in DLBCL. The results of this doctoral thesis unravel a cooperation between CXCR4 and MYC in DLBCL, and indicate that CXCR4 inhibition in combination with inhibition of MYC is a promising novel therapeutic approach in DLBCL. |
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