Publications by authors named "L B Abrahmsen"
Article Synopsis
- - Metastatic prostate cancer is difficult to treat due to malfunctioning of the p53 protein, which normally helps control cancer growth, and mutations in p53 can prevent successful treatment efforts.
- - Research focused on alternative cancer drivers led to the discovery that MDM4 plays a significant role in prostate cancer cells, showing that reducing MDM4 can inhibit cancer cell growth by triggering cell death or senescence.
- - Targeting MDM4's effects can be enhanced in prostate cancers with mutated p53 by using a new small molecule drug that reactivates p53 and increases oxidative stress, promoting cancer cell death.
In response to genotoxic stress, the tumor suppressor p53 acts as a transcription factor by regulating the expression of genes critical for cancer prevention. Mutations in the gene encoding p53 are associated with cancer development. PRIMA-1 and eprenetapopt (APR-246/PRIMA-1) are small molecules that are converted into the biologically active compound, methylene quinuclidinone (MQ), shown to reactivate mutant p53 by binding covalently to cysteine residues.
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- Asparaginase is a key treatment for acute lymphoblastic leukemia (ALL) because it lowers blood asparagine levels, which ALL cells need to survive, but resistance can develop due to the enzyme asparagine synthetase (ASNS) that produces asparagine from within the cell.
- Mutations in the TP53 gene are rare in ALL but are linked to poorer treatment responses, particularly in relapsed cases, and the compound APR-246 is being tested in clinical trials for its ability to reactivate mutant p53.
- New data suggest APR-246 may directly or indirectly target ASNS, and when used in combination with asparaginase, it enhances cancer cell growth suppression, indicating a promising new
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. APR-246 is currently tested in a phase III clinical trial in myelodysplastic syndrome (MDS).
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