PARP Inhibitor Articles

Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S.

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 muscle invasive form of urothelial bladder cancer (UBC) is a deadly disease. Currently, the therapeutic approach of UBC is mostly based on surgery and standard chemotherapy. Biomarkers to establish appropriate drugs usage are missing.

Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients.

PARP inhibitors (PARPi) are established treatments for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) deficiency after androgen receptor signalling inhibitor (ARSI) failure.

Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, are being explored as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) in men harboring mutations in homologous recombination DNA-repair genes.

ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC).

Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID.

The PROfound trial evaluated the PARP inhibitor olaparib in metastatic castration-resistant prostate cancers harboring alterations in BRCA1/2 and ATM (cohort A) and in 12 other homologous recombination repair genes (cohort B).

Cancers with mutations in BRCA2 have defective DNA repair capacity which is potentially targetable with poly-ADP(ribose) polymera se (PARP) inhibitors such as olaparib and rucaparib. However, the development of a secondary mutation that restores BRCA2 function is a well-documented mechanism of resistance to PARP inhibitors.

Prostate cancer heritability is attributed to a combination of rare, moderate to highly penetrant genetic variants as well as commonly occurring variants conferring modest risks [single nucleotide polymorphisms (SNPs)].

Herein, we analyze answers achieved, open questions, and future perspectives regarding the analysis of the pathogenetic variants (PV) of DNA damage response (and repair) (DDR) genes in prostate cancer (PC) patients.

The recent approval of PARP inhibitors for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA mutations firstly introduced the possibility of proposing a targeted treatment in this disease.

Metastatic prostate cancer is a heterogeneous disease characterized by clinical and genomic heterogeneity. Many prostate cancers harbor mutations causing DNA repair deficiency, specifically homologous recombination deficiency, sensitizing to drugs that inhibit poly ADP-ribose polymerase (PARP).

Olaparib + abiraterone has a combined antitumor effect in metastatic castration-resistant prostate cancer (mCRPC), but the efficacy of this combination in patients with DNA damage repair (DDR)-deficient mCRPC progressing after abiraterone is unknown.

Polyadenosine-diphosphate-ribose polymerase (PARP) inhibitors cause deoxyribonucleic acid (DNA) damage that can be lethal to cells with deficient repair mechanisms. A number of PARP inhibitors are being tested as treatments for men with prostate cancer, both as monotherapies and in combinations that are based on purported synergies in treatment effect.

PARP inhibitors appear to offer a promising role in the accompaniment of many of the cytotoxic agents used in the present day to combat cancer proliferation in BRCA1/2 deficient tumors. Current species of PARP inhibitors have yet to demonstrate a superior effect to that of existing therapies when administered as a single agent; however, they have appeared to amplify the effect of these existing chemotherapies when utilized together.

The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve "synthetic lethality" in treating this fatal disease.

Despite remarkable progress in the last decade, metastatic prostate cancer (mPCa) remains incurable. The approval of PARP inhibitors (PARPis) represents a milestone in this field, which definitively enters the era of precision medicine, as mPCa is often enriched for defects of homologous recombination repair genes.

Androgen deprivation therapy (ADT) plus Androgen Receptor Target Agents (ARTAs) or docetaxel are the actual standard of care in prostate cancer (PC) first-line therapy. Several therapeutic options are currently available for pretreated patients: cabazitaxel, olaparib and rucaparib for BRCA mutations, Radium-223 for selected patients with symptomatic bone metastasis, sipuleucel T and 177 Lu-PSMA-617.

This review will provide an overview of the use rucaparib and olaparib in patients with metastatic castration resistant prostate cancer (mCRPC) with the goal to assist the clinician's decision-making process when considering these agents for an individual patient.

Solid tumors harboring BRCA1 or BRCA2 mutations have been shown to respond to PARP inhibitors. These responses are partial and transient. In this case report, we describe an 82-year-old male with poorly differentiated prostate cancer with metastases to the lung, liver, abdomen, and bowel.

The introduction of novel therapeutic agents for advanced prostate cancer has led to a wide range of treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). In the past decade, new treatment options for mCRPC, including abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, 177Lu-PSMA-617, and Olaparib, have demonstrated a survival benefit in phase 3 trials.

Poly(ADP-ribose) polymerase (PARP) inhibitors in combination with androgen-receptor signaling inhibitors are a promising therapeutic option for patients with metastatic castration-sensitive prostate cancer (mCSPC) and homologous recombination repair (HRR) gene alterations.

PARP inhibitors in combination with androgen receptor-targeted therapy have demonstrated potential in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Here, we describe the design and rationale of the multinational, Phase III, two-part TALAPRO-2 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide as a first-line treatment for patients with mCRPC with or without DNA damage response (DDR) alterations.

The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib.

In May 2020, the approval of rucaparib (a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor) in the USA marked the arrival of a new class of targeted, life-prolonging therapeutics for the 15-25% of metastatic castration-resistant prostate cancer patients whose tumors harbor germline or somatic BRCA1/2 gene alterations.

An estimated one-fifth or more of metastatic castration-resistant prostate cancer (mCRPC) harbor defects in genes involved in DNA repair pathway (e.g., BRCA2, BRCA1, and others). Early evidence suggests these alterations may be predictive of therapeutic response to PARP inhibitors and platinum chemotherapy, thought to reflect principles of synthetic lethality and are currently being investigated in an increasing number of prospective clinical trials.

Immune checkpoint inhibitors (ICIs) have become key agents in the management of clear cell renal cell carcinoma (ccRCC), but their benefits are limited and responders remain unidentified. We investigated the significance of PARP1 in ccRCC using RNA sequencing data for 311 tumors from patients enrolled in prospective clinical trials of PD-1 blockade.

The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib was approved in the United States based on the phase 2 TRITON2 study of patients with BRCA1 or BRCA2 (BRCA)-mutated metastatic castration-resistant prostate cancer (mCRPC).