Effects of the Mutant TP53 Reactivator APR-246 on Therapeutic Sensitivity of Pancreatic Cancer Cells in the Presence and Absence of WT-TP53 [PDF]
Cells, 2022 The TP53 tumor suppressor is mutated in ~75% of pancreatic cancers. The mutant TP53 protein in pancreatic ductal adenocarcinomas (PDAC) promotes tumor growth and metastasis.
Stephen L. Abrams +13 more
doaj +5 more sources
A thiol‐bound drug reservoir enhances APR‐246‐induced mutant p53 tumor cell death [PDF]
EMBO Molecular Medicine, 2020 The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance.
Sophia Ceder +15 more
doaj +4 more sources
Synergistic effects of PRIMA-1Met (APR-246) and 5-azacitidine in TP53-mutated myelodysplastic syndromes and acute myeloid leukemia [PDF]
Haematologica, 2020 Myelodysplastic syndromes and acute myeloid leukemia with TP53 mutations are characterized by frequent relapses, poor or short responses, and poor survival with the currently available therapies including chemotherapy and 5-azacitidine (AZA).
Nabih Maslah +16 more
doaj +5 more sources
APR-246 induces early cell death by ferroptosis in acute myeloid leukemia [PDF]
Haematologica, 2021 APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). APR-246 reactivates the transcriptional activity of p53 mutants by facilitating their binding to DNA target ...
Rudy Birsen +15 more
doaj +3 more sources
Immunotherapy against the Cystine/Glutamate Antiporter xCT Improves the Efficacy of APR-246 in Preclinical Breast Cancer Models [PDF]
Biomedicines, 2022 Breast cancer is the most frequent cancer in women. Despite recent clinical advances, new therapeutic approaches are still required. The cystine-glutamate antiporter xCT, encoded by the SLC7A11 gene, which imports cystine in exchange with glutamate, is a
Giuseppina Barutello +6 more
doaj +2 more sources
Therapeutic targeting of mutant p53 in pediatric acute lymphoblastic leukemia [PDF]
Haematologica, 2020 Alterations of the tumor suppressor gene TP53 are found in different cancers, in particular in carcinomas of adults. In pediatric acute lymphoblastic leukemia (ALL), TP53 mutations are infrequent but enriched at relapse.
Salih Demir +13 more
doaj +3 more sources
Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies [PDF]
Cells, 2021 The cystine/glutamate antiporter xCT is a tumor-associated antigen that has been newly identified in many cancer types. By participating in glutathione biosynthesis, xCT protects cancer cells from oxidative stress conditions and ferroptosis, and ...
Jolanda Magri +7 more
doaj +3 more sources
Transketolase regulates sensitivity to APR-246 in p53-null cells independently of oxidative stress modulation [PDF]
Scientific Reports, 2021 The prevalence and dire implications of mutations in the tumour suppressor, p53, highlight its appeal as a chemotherapeutic target. We recently showed that impairing cellular antioxidant systems via inhibition of SLC7A11, a component of the system xc ...
Julia V. Milne +5 more
doaj +2 more sources
Neuroblastoma response to RAS-MAPK inhibitors and APR-246 (eprenetapopt) co-treatment is dependent on SLC7A11 [PDF]
Frontiers in OncologyBackgroundWe previously demonstrated that APR-246 (eprenetapopt) could be an efficient treatment option against neuroblastoma (NB), the most common pediatric extracranial solid tumor.
Vid Mlakar +10 more
doaj +2 more sources
APR-246 increases tumor antigenicity independent of p53 [PDF]
Life Science AllianceMichels, Venkatesh et al demonstrate that APR-246, a small molecule Michael acceptor, enhances tumor immunogenicity. Combination of APR-246 with immune modulation enhances antitumor responses.
Judith Michels +15 more
doaj +2 more sources