Biomaterial Database

Homologous Recombination Repair Deficiency in Metastatic Prostate Cancer: New Therapeutic Opportunities. 2024

Claudia Piombino, and Stefania Pipitone, and Elena Tonni, and Luciana Mastrodomenico, and Marco Oltrecolli, and Cyrielle Tchawa, and Rossana Matranga, and Sara Roccabruna, and Elisa D'Agostino, and Marta Pirola, and Francesca Bacchelli, and Cinzia Baldessari, and Maria Cristina Baschieri, and Massimo Dominici, and Roberto Sabbatini, and Maria Giuseppa Vitale

Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41124 Modena, Italy.

More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009362	Neoplasm Metastasis	The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.	Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D010793	Phthalazines	Bicyclic heterocyclic compounds containing a BENZENE ring fused to PYRIDAZINE.
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011471	Prostatic Neoplasms	Tumors or cancer of the PROSTATE.	Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D011944	Receptors, Androgen	Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.	Androgen Receptors,5 alpha-Dihydrotestosterone Receptor,Androgen Receptor,Dihydrotestosterone Receptors,Receptor, Testosterone,Receptors, Androgens,Receptors, Dihydrotestosterone,Receptors, Stanolone,Stanolone Receptor,Testosterone Receptor,5 alpha Dihydrotestosterone Receptor,Androgens Receptors,Receptor, 5 alpha-Dihydrotestosterone,Receptor, Androgen,Receptor, Stanolone,Stanolone Receptors,alpha-Dihydrotestosterone Receptor, 5
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067856	Poly(ADP-ribose) Polymerase Inhibitors	Chemicals and drugs that inhibit the action of POLY(ADP-RIBOSE)POLYMERASES.	Inhibitors of Poly(ADP-ribose) Polymerase,PARP Inhibitor,Poly(ADP-Ribose) Polymerase Inhibitor,Poly(ADP-ribosylation) Inhibitor,Inhibitors of Poly(ADP-ribose) Polymerases,PARP Inhibitors,Poly(ADP-ribosylation) Inhibitors,Inhibitor, PARP,Inhibitors, PARP
D059767	Recombinational DNA Repair	Repair of DNA DAMAGE by exchange of DNA between matching sequences, usually between the allelic DNA (ALLELES) of sister chromatids.	Homologous Recombination DNA Repair,Homologous Recombination Repair of DNA,Homology-Directed dsDNA Break Repair,Homologous Recombination Double-Stranded Break DNA Repair,Homologous Recombination Repair,Homologous Recombinational Repair,Recombination Repair,Recombinational Repair of DNA,DNA Recombinational Repair,DNA Repair, Recombinational,Homologous Recombination Double Stranded Break DNA Repair,Homologous Recombinational Repairs,Homology Directed dsDNA Break Repair,Recombination Repair, Homologous,Recombinational Repair, Homologous,Repair, Homologous Recombinational,Repair, Recombination,Repair, Recombinational DNA
D019313	BRCA1 Protein	The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). It contains an N-terminal RING FINGER DOMAIN and is a PROTEIN PHOSPHATASE 1 regulatory subunit. In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)	BRCA1 Gene Product,Breast Cancer 1 Gene Product,Breast Cancer 1 Protein,Breast Cancer Type 1 Susceptibility Protein,Ring Finger Protein 53