Abstract 276: Enhancing standard chemotherapy response by targeted inhibition of MAPK signaling pathways in experimental pancreatic cancer
| Autor: | Margaret A. Schwarz, Sheena Monahan, Niranjan Awasthi, Roderich E. Schwarz |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Trametinib
Cancer Research Chemotherapy endocrine system diseases Oncogene business.industry medicine.medical_treatment Cancer medicine.disease medicine.disease_cause Gemcitabine chemistry.chemical_compound Oncology Paclitaxel chemistry Pancreatic cancer Cancer research medicine KRAS business medicine.drug |
| Zdroj: | Cancer Research. 76:276-276 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all solid tumors, with an overall survival rate of less than 6%. Gemcitabine (Gem) remained the standard of care agent over the past 16 years despite limited clinical benefits. Nab-paclitaxel (NPT), a water-soluble albumin-bound formulation of paclitaxel, has recently shown greater efficacy in advanced PDAC. Nab-paclitaxel combination with gemcitabine is now standard of care for advanced PDAC. More than 90% of PDAC tumors harbor an activating mutation in the KRAS oncogene. Since to date no therapeutics have effectively targeted this oncogene product, alternative strategies focus on inhibition of downstream effectors of KRAS signaling pathways. Trametinib (Tra) is a small molecule inhibitor of the RAF-MEK-ERK (MAPK) signaling pathway that is a well-described mediator of KRAS induced transformation and tumorigenesis. In the present preclinical study, we evaluated combination treatment benefits of the standard chemotherapeutics with trametinib to define a novel therapeutic strategy for PDAC. Median animal survival over controls (20 days) in human intraperitoneal PDAC xenografts was significantly improved by NPT (33 days, a 65% increase, p = 0.0004), Gem (26 days, a 30% increase, p = 0.002), NPT+Gem (39 days, a 95% increase, p = 0.0001) and Tra (31 days, a 55% increase, p = 0.0004) therapy. Survival was further increased by addition of trametinib to chemotherapy: NPT+Tra (median: 37 days, a 85% increase, p = 0.0001), Gem+Tra (34 days, a 70% increase, p = 0.0001) and NPT+Gem+Tra (49 days, a 145% increase, p Citation Format: Niranjan Awasthi, Sheena Monahan, Margaret A. Schwarz, Roderich E. Schwarz. Enhancing standard chemotherapy response by targeted inhibition of MAPK signaling pathways in experimental pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 276. |
| Databáze: | OpenAIRE |
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