c-FLIP is a key anti-apoptotic factor that is over-expressed in many tumors and blocks the apoptotic machinery by interfering with FADD, caspase-8 and DR5. Significant evidence demonstrates that c-FLIP over-expression in tumors is a major cause of resistance to TRAIL-induced apoptosis. Therefore, strategies to inhibit c-FLIP action and to overcome c-FLIP-induced resistance in tumor cells may lead to novel and more effective therapies. We have discovered a bioactive peptide, ApoFLIP that antagonizes with c-FLIP and reinstates the apoptotic machinery in c-FLIP expressing cells. The major goal of this proposal is to develop and characterize drug-like variants of this peptide. These agents could provide significant enhancements in the current therapeutic strategies in hematological malignancies and other tumors that show resistance to apoptosis-inducing therapeutics.
This proposal focuses on characterization and enhancement of a novel bioactive peptide, ApoFLIP, recently discovered by us that could remove a major apoptotic block in cancer cells and sensitize them to apoptosis. ApoFLIP thus provides an innovative therapeutic strategy for cancer.
|Bhasin, Manoj K; Ndebele, Kenneth; Bucur, Octavian et al. (2016) Meta-analysis of transcriptome data identifies a novel 5-gene pancreatic adenocarcinoma classifier. Oncotarget 7:23263-81|
|Bucur, Octavian; Gaidos, Gabriel; Yatawara, Achani et al. (2015) A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death. Sci Rep 5:9893|
|Bucur, Octavian; Stancu, Andreea Lucia; Muraru, Maria Sinziana et al. (2014) PLK1 is a binding partner and a negative regulator of FOXO3 tumor suppressor. Discoveries (Craiova) 2:|
|Pennarun, B; Gaidos, G; Bucur, O et al. (2013) killerFLIP: a novel lytic peptide specifically inducing cancer cell death. Cell Death Dis 4:e894|
|Bucur, Octavian; Stancu, Andreea Lucia; Goganau, Ioana et al. (2013) Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells. PLoS One 8:e77390|
|Bucur, Octavian; Pennarun, Bodvael; Stancu, Andreea Lucia et al. (2013) Poor antibody validation is a challenge in biomedical research: a case study for detection of c-FLIP. Apoptosis 18:1154-62|
|Bucur, O; Stancu, A L; Khosravi-Far, R et al. (2012) Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications. Cell Death Dis 3:e263|
|Singh, Amrik; Plati, Jessica; Khosravi-Far, Roya (2011) Harnessing the tumor suppressor function of FOXO as an alternative therapeutic approach in cancer. Curr Drug Targets 12:1311-21|
|Plati, Jessica; Bucur, Octavian; Khosravi-Far, Roya (2011) Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb) 3:279-96|
|Degli Esposti, Mauro; Tour, Julien; Ouasti, Sihem et al. (2009) Fas death receptor enhances endocytic membrane traffic converging into the Golgi region. Mol Biol Cell 20:600-15|
Showing the most recent 10 out of 22 publications