The TP53 tumor suppressor is the most frequently altered gene in human cancers, and has been a major focus of oncology research. The p53 protein is a transcription factor that can activate the expression of multiple target genes and plays critical roles in regulating cell cycle, apoptosis, and genomic stability, and is widely regarded as the "guardian of the genome". Accumulating evidence has shown that p53 also regulates cell metabolism, ferroptosis, tumor microenvironment, autophagy and so on, all of which contribute to tumor suppression. Mutations in TP53 not only impair its tumor suppressor function, but also confer oncogenic properties to p53 mutants. Since p53 is mutated and inactivated in most malignant tumors, it has been a very attractive target for developing new anti-cancer drugs. However, until recently, p53 was considered an "undruggable" target and little progress has been made with p53-targeted therapies. Here, we provide a systematic review of the diverse molecular mechanisms of the p53 signaling pathway and how TP53 mutations impact tumor progression. We also discuss key structural features of the p53 protein and its inactivation by oncogenic mutations. In addition, we review the efforts that have been made in p53-targeted therapies, and discuss the challenges that have been encountered in clinical development. 

/pdf/targeting-p53-pathways-mechanisms-structures-and-advances-in-4lz29aui.pdf

Targeting p53 pathways: mechanisms, structures, and advances in therapy

Genetic Risk Prediction for Prostate Cancer: Implications for Early Detection and Prevention.

Germline TP53 pathogenic variants and breast cancer: A narrative review.

An important fraction (>/~10%) of men with high‐risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases.

Germline genetics of prostate cancer

http://manuscript.elsevier.com/S0304383522001938/pdf/S0304383522001938.pdf

Precision intervention for prostate cancer: Re-evaluating who is at risk.

Association of Inherited Mutations in DNA Repair Genes with Localized Prostate Cancer.

Inherited TP53 Variants and Risk of Prostate Cancer

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Association of Inherited Mutations in DNA Repair Genes with Localized Prostate Cancer.

Inherited TP53 Variants and Risk of Prostate Cancer