PARP Articles

Genetic instability is one part of the oncogenic process. Gene mutations involved in DNA repair mechanisms can promote this genetic instability and participate in oncogenesis and metastatic progression.

For decades, the treatment of advanced prostate cancer was mainly based on the manipulation of the androgen receptor-controlled proliferation pathway. Chemotherapy only played an additional important role with the advent of taxanes.

Both germline and somatic BReast CAncer gene (BRCA) mutations are poor prognostic markers in men with localized or metastatic prostate cancer. For instance, men with these mutations often are diagnosed with prostate cancer earlier and develop metastatic disease earlier compared with those who do not harbor similar mutations.

Androgen deprivation therapy (ADT) is a powerful treatment for metastatic hormone-sensitive prostate cancer (mHSPC) patients, but eventually and inevitably, cancer relapses, progressing to the fatal castration-resistant (CR)PC stage.

Poly-ADP ribose polymerase (PARP) inhibitors are currently used in the treatment of several cancers carrying mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2, with many more potential applications under study and in clinical trials.

The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2) mutations are implicated in the highest risk of prostate cancer (PC) predisposition and aggressiveness.

Poly (ADP-ribose) polymerase inhibitors (PARPi) were initially deployed to target breast and ovarian tumors with mutations in DNA damage response genes. Recently, PARPi have been shown to be beneficial in the treatment of prostate cancer (PC) patients having exhausted conventional therapeutics.

Although recent advances in the treatment of castration-resistant prostate cancer (CRPC) have significantly improved patient outcomes, advanced prostate cancer is still associated with substantial morbidity and mortality, particularly in patients who develop resistance after multiple lines of therapy.

Prostate cancers that progress despite androgen deprivation develop into castration-resistant prostate cancer, a fatal disease with few treatment options. In this review, we discuss the current understanding of prostate cancer subtypes and alterations in the DNA damage response (DDR) that can predispose to the development of prostate cancer and affect its progression.

Recent studies have provided a better understanding of the molecular underpinnings of prostate cancer. Alterations in genes encoding for proteins involved in the different pathways in charge of preserving genomic integrity and repairing DNA damage are common in prostate cancer, particularly in late-stage disease.

PARP inhibitors (PARPi) have recently emerged as a new treatment option for several solid tumors, including metastatic castration-resistant prostate cancer (mCRPC). However, several grade 3-4 adverse events have been reported during PARPi administration, leading to limitations in treatment adherence.

PARP inhibitor (PARPi) therapy is approved for patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) genomic aberrations. However, only a fraction of patients with BRCA1/2 mutations respond to PARPi therapy.

Prostate cancer (PCa) is a disease of mutated and misregulated genes. However, primary prostate tumors have relatively few mutations, and only three genes ( ERG, PTEN, and SPOP) are recurrently mutated in more than 10% of primary tumors.

Genomic studies of localized and metastatic prostate cancer have identified a high prevalence of clinically actionable alterations including mutations in DNA repair genes. In this manuscript, we review the current knowledge on DNA repair defects in prostate cancer and provide an overview of how these alterations can be targeted towards a personalized prostate cancer management.

Castration-resistant prostate cancer (PCa) represents a serious health challenge. Based on mechanistically-supported rationale we explored new therapeutic options based on clinically available drugs with anticancer effects, including inhibitors of PARP1 enzyme (PARPi), and histone deacetylases (vorinostat), respectively, and disulfiram (DSF, known as alcohol-abuse drug Antabuse) and its copper-chelating metabolite CuET that inhibit protein turnover.

For about a decade, poly [ADP ribose] polymerases (PARP) inhibitors have been used almost exclusively to treat tumours that are deficient in one of the BRCA genes. In advanced prostate cancer, which is largely driven by the activity of the androgen receptor (AR), accumulating preclinical evidence has suggested an interplay between the AR and PARP, which could be therapeutically exploited independently of defects in the tumour's DNA homologous recombination repair (HRR) machinery.