<scp>PARP</scp> inhibition in prostate cancer

Nientiedt, Cathleen; Duensing, Anette; Zschäbitz, Stefanie; Jäger, Dirk; Hohenfellner, Markus; Duensing, Stefan

doi:10.1002/gcc.22903

Cited by 4 publications

(6 citation statements)

References 60 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other major cancer types where PARP inhibitors and combinatorial therapies are being developed and recent trials showed encouraging results include breast, pancreatic and prostate cancer. Reviews by Ali et al, 37 Singh et al 38 and Nientiedt et al 39 thoroughly describe recent clinical and diagnostic data in these cancer types and provide an outlook on future developments. Future clinical trials will show whether this therapeutic approach can be extended to other cancer types, possibly also in conjunction with other therapies including checkpoint blockers 40 .…”

Section: Figurementioning

confidence: 99%

Homologous recombination repair deficiency (HRD): From biology to clinical exploitation

González

2021

Genes Chromosomes & Cancer

Self Cite

View full text Add to dashboard Cite

Section: Figurementioning

confidence: 99%

Homologous recombination repair deficiency (HRD): From biology to clinical exploitation

González

2021

Genes Chromosomes & Cancer

Self Cite

View full text Add to dashboard Cite

“…Olaparib (Lynparza) is a small, oral, and bioavailable molecule that selectively binds and inhibits PARP [162] . Mateo et al [134] published two Phase II clinical trials, "TOPARP-A" (NCT01682772) and "TOPARP-B" (NCT01682772), involving patients with mCRPC who had previously received standard treatments and who were treated with olaparib.…”

Section: Parp Inhibitorsmentioning

confidence: 99%

“…Both studies demonstrated that patients with defective DDR genes and who were no longer responding to the current treatments exhibited a high response rate to olaparib. Importantly, response to treatment seemed dependent on specific DDR gene defects, as the highest response was achieved in the BRCA1/2 aberrant subgroup [ 133 , 134 , 163 ] .…”

Section: Emerging Treatments Targeting Mcrpcmentioning

confidence: 99%

Drug resistance in metastatic castration-resistant prostate cancer: an update on the status quo

Yehya¹,

Ghamlouche²,

Zahwe³

et al. 2022

Cancer Drug Resist

View full text Add to dashboard Cite

Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality in men globally. Despite improvements in the diagnosis and treatment of PCa, a significant proportion of patients with high-risk localized disease and all patients with advanced disease at diagnosis will experience progression to metastatic castration-resistant prostate cancer (mCRPC). Multiple drugs are now approved as the standard of care treatments for patients with mCRPC that have been shown to prolong survival. Although the majority of patients will respond initially, primary and secondary resistance to these therapies make mCRPC an incurable disease. Several molecular mechanisms underlie the development of mCRPC, with the androgen receptor (AR) axis being the main driver as well as the key drug target. Understanding resistance mechanisms is crucial for discovering novel therapeutic strategies to delay or reverse the progression of the disease. In this review, we address the diverse mechanisms of drug resistance in mCRPC. In addition, we shed light on emerging targeted therapies currently being tested in clinical trials with promising potential to overcome mCRPC-drug resistance.

show abstract

“…Although the mechanisms underlying tumor cell migration and invasion have been extensively studied [4], relatively little is known about whether, and to what extent, recurrent genetic alterations modulate these activities. In prostate cancer, there is compelling evidence that mutations in genes involved in the homologous recombination-mediated repair (HRR) of DNA double-strand breaks, most notably BRCA2, define a subset of patients with a therapeutic vulnerability to PARP inhibition and platinum compounds [5][6][7]. This subgroup of men with prostate cancer also shows distinct clinical characteristics, including a higher rate of lymph node and distant metastasis and poorer patient survival outcomes [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Deficiency in DNA Damage Repair Proteins Promotes Prostate Cancer Cell Migration through Oxidative Stress

Lantwin,

Kaczorowski,

Nientiedt

et al. 2024

Onco

Self Cite

View full text Add to dashboard Cite

Introduction: DNA damage repair gene deficiency defines a subgroup of prostate cancer patients with early metastatic progression and unfavorable disease outcome. Whether deficiency in DNA damage repair genes directly promotes metastatic dissemination is not completely understood. Methods: The migratory behavior of prostate cancer cells was analyzed after siRNA-mediated knockdown of DNA damage repair and checkpoint proteins, including BRCA2, ATM, and others, using transwell migration assays, scratch assays and staining for F-actin to ascertain cell circularity. Cells deficient in BRCA2 or ATM were tested for oxidative stress by measuring reactive oxygen species (ROS). The effects of ROS inhibition on cell migration were analyzed using the antioxidant N-acetylcysteine (NAC). The correlation between BRCA2 deficiency and oxidative stress was ascertained via immunohistochemistry for methylglyoxal (MG)-modified proteins in 15 genetically defined primary prostate cancers. Results: Prostate cancer cells showed a significantly increased migratory activity after the knockdown of BRCA2 or ATM. There was a significant increase in ROS production in LNCaP cells after BRCA2 knockdown and in PC-3 cells after BRCA2 or ATM knockdown. Remarkably, the ROS scavenger NAC abolished the enhanced motility of prostate cancer cells after the knockdown of BRCA2 or ATM. Primary prostate cancers harboring genetic alterations in BRCA2 showed a significant increase in MG-modified proteins, indicating enhanced oxidative stress in vivo. Conclusions: Our results indicate that DNA damage repair gene deficiency may contribute to the metastatic dissemination of prostate cancer through enhanced tumor cell migration involving oxidative stress.

show abstract

PARP inhibition in prostate cancer

Cited by 4 publications

References 60 publications

Homologous recombination repair deficiency (HRD): From biology to clinical exploitation

Homologous recombination repair deficiency (HRD): From biology to clinical exploitation

Drug resistance in metastatic castration-resistant prostate cancer: an update on the status quo

Deficiency in DNA Damage Repair Proteins Promotes Prostate Cancer Cell Migration through Oxidative Stress

Contact Info

Product

Resources

About