Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer.
Shengliang ZhangLindsey CarlsenLiz Hernandez BorreroAttila A SeyhanXiaobing TianWafik S El-DeiryPublished in: Biomolecules (2022)
TP53 is a tumor suppressor gene that encodes a sequence-specific DNA-binding transcription factor activated by stressful stimuli; it upregulates target genes involved in growth suppression, cell death, DNA repair, metabolism, among others. TP53 is the most frequently mutated gene in tumors, with mutations not only leading to loss-of-function (LOF), but also gain-of-function (GOF) that promotes tumor progression, and metastasis. The tumor-specific status of mutant p53 protein has suggested it is a promising target for cancer therapy. We summarize the current progress of targeting wild-type and mutant p53 for cancer therapy through biotherapeutic and biopharmaceutical methods for (1) boosting p53 activity in cancer, (2) p53-dependent and p53-independent strategies for targeting p53 pathway functional restoration in p53-mutated cancer, (3) targeting p53 in immunotherapy, and (4) combination therapies targeting p53, p53 checkpoints, or mutant p53 for cancer therapy.
Keyphrases
- cancer therapy
- wild type
- drug delivery
- papillary thyroid
- dna repair
- dna binding
- transcription factor
- cell death
- squamous cell
- squamous cell carcinoma
- gene expression
- lymph node metastasis
- genome wide
- childhood cancer
- signaling pathway
- genome wide identification
- dna methylation
- amino acid
- long non coding rna
- pi k akt
- binding protein
- cell cycle arrest