Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Targeting liposarcoma by various therapeutic approaches with concurrent exploitation of genetic aberrations
Following the failure of the standard modalities (surgery, chemotherapy, and radiotherapy) for long-term eradication of tumors, tumor-specific targeted therapies emerged for the treatment of patients with liposarcoma in particular of subtype welldifferentiated/de-differentiated (WD/DDLPS). Therapeutic approaches with single agents targeting the activity of the key disease-related oncogene products MDM2 or CDK4 displayed encouraging results. However, the clinical efficacy of these pharmacological inhibitors is still quite limited. To this end, based on the presence of the genetic abnormalities, several rationales were designed to combine such inhibitors with concurrent application of existing therapies (radiotherapy, immunotherapy) in order to achieve an improved response. In parallel, the therapy-driven modulation of signaling pathways and phenotypic cellular fates were studied in a set of liposarcomaderived cell lines in vitro. Based on the presence of key oncogenes, it was examined whether co-inhibition of CDK4 and MDM2 led to an enhanced anti-proliferative efficacy in liposarcoma cell lines. The findings of the study demonstrated unperturbed signaling pathways with non-additive effects by co-inhibition. This study also indicated MDM2-mediated degradation of the retinoblastoma (RB) protein, which might have rendered the cells insensitive to CDK4 inhibitors. However, sequence alteration of inhibitors revealed no significant enhancement of growth inhibition, which indicated RB degradation not to be the primary cause of observed non-additivity. Thus, it could be stated that co-targeting of CDK4 and MDM2 might not exert a synergistic growth inhibition in liposarcoma cells. Next, it was evaluated whether MDM2 inhibition in TP53 wild-type liposarcoma cell lines enhanced the susceptibility of tumor cells to the treatment with ionizing radiation. It was hypothesized that MDM2 inhibition would disrupt the MDM2-p53 interaction and reactivate the wild-type functional p53. Addition of radiation treatment would further ...
Targeting liposarcoma by various therapeutic approaches with concurrent exploitation of genetic aberrations
Following the failure of the standard modalities (surgery, chemotherapy, and radiotherapy) for long-term eradication of tumors, tumor-specific targeted therapies emerged for the treatment of patients with liposarcoma in particular of subtype welldifferentiated/de-differentiated (WD/DDLPS). Therapeutic approaches with single agents targeting the activity of the key disease-related oncogene products MDM2 or CDK4 displayed encouraging results. However, the clinical efficacy of these pharmacological inhibitors is still quite limited. To this end, based on the presence of the genetic abnormalities, several rationales were designed to combine such inhibitors with concurrent application of existing therapies (radiotherapy, immunotherapy) in order to achieve an improved response. In parallel, the therapy-driven modulation of signaling pathways and phenotypic cellular fates were studied in a set of liposarcomaderived cell lines in vitro. Based on the presence of key oncogenes, it was examined whether co-inhibition of CDK4 and MDM2 led to an enhanced anti-proliferative efficacy in liposarcoma cell lines. The findings of the study demonstrated unperturbed signaling pathways with non-additive effects by co-inhibition. This study also indicated MDM2-mediated degradation of the retinoblastoma (RB) protein, which might have rendered the cells insensitive to CDK4 inhibitors. However, sequence alteration of inhibitors revealed no significant enhancement of growth inhibition, which indicated RB degradation not to be the primary cause of observed non-additivity. Thus, it could be stated that co-targeting of CDK4 and MDM2 might not exert a synergistic growth inhibition in liposarcoma cells. Next, it was evaluated whether MDM2 inhibition in TP53 wild-type liposarcoma cell lines enhanced the susceptibility of tumor cells to the treatment with ionizing radiation. It was hypothesized that MDM2 inhibition would disrupt the MDM2-p53 interaction and reactivate the wild-type functional p53. Addition of radiation treatment would further ...
Targeting liposarcoma by various therapeutic approaches with concurrent exploitation of genetic aberrations
Das, Samayita (Autor:in) / Thomale, Jürgen
12.10.2021
Hochschulschrift
Elektronische Ressource
Englisch
Orbit liposarcoma revealed by proptosis: a case report
| British Library Conference Proceedings | 2006
Review on the Exploitation Approaches of Tidal Power
| British Library Conference Proceedings | 2013
Huge retroperitoneal liposarcoma encasing right kidney: A case report from Nepal
| Elsevier | 2022