Purpose Of Review: In the past few years, the advent of PARP inhibitors has been a revolution in the management of ovarian cancer. Patients harboring somatic or germ line BRCA1/2 mutations exhibit different clinical and treatment response behavior. The BRCA gene is involved in repairing DNA repair via homologous recombination, and mutation of this gene leads to homologous recombination deficiency (HRD).

Recent Findings: HRD constitutes a therapeutic opportunity for these patients, thanks to the development of poly(ADP-ribose) polymerase inhibitors (PARPi) in the late 2000s. Indeed, using PARPi in patients with HRD simultaneously compromises two mechanisms of DNA repair, resulting in synthetic lethality.

Summary: This breakthrough in clinical practice has raised remaining questions: which population will most benefit from PARPi? Are all ovarian cancers susceptible to synthetic lethal strategy? At which stage of ovarian cancer should PARPi be used? Is earlier always better? Are PARPi all equivalent? Which strategies are reasonable to overcome PARPi resistance? Which combination strategies should be efficient?

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCO.0000000000000557DOI Listing

Publication Analysis

Top Keywords

polyadp-ribose polymerase
12
polymerase inhibitors
8
ovarian cancer
8
dna repair
8
homologous recombination
8
parpi
5
current role
4
role polyadp-ribose
4
inhibitors polyadp-ribose
4
polymerase inhibitor
4

Similar Publications

The pollution by heavy metals in coastal waters has gradually intensified due to industrial development. In this study, physiological responses of Ulva lactuca, one of the most common green seaweeds with important ecological and economic value in the global intertidal zone, to acute copper stress were investigated. Results showed that an increase in copper ions concentration significantly inhibited photosynthetic activity and inorganic nitrogen utilization by U.

View Article and Find Full Text PDF

Objective: We assessed real-world trends in the use of maintenance therapy [MT] (i.e., polyADP-ribose polymerase inhibitors (PARPi) and/or bevacizumab following platinum-based chemotherapy), among U.

View Article and Find Full Text PDF

Activation of retinoid X receptors protects retinal neurons and pigment epithelial cells from BMAA-induced death.

Biochim Biophys Acta Mol Cell Res

December 2024

Instituto de Investigaciones Bioquímicas de Bahía Blanca, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Argentina. Electronic address:

Exposure to the non-protein amino acid cyanotoxin β-N-methylamino-L-alanine (BMAA), released by cyanobacteria found in many water reservoirs has been associated with neurodegenerative diseases. We previously demonstrated that BMAA induced cell death in both retina photoreceptors (PHRs) and amacrine neurons by triggering different molecular pathways, as activation of NMDA receptors and formation of carbamate-adducts was only observed in amacrine cell death. We established that activation of Retinoid X Receptors (RXR) protects retinal cells, including retina pigment epithelial (RPE) cells from oxidative stress-induced apoptosis.

View Article and Find Full Text PDF

Genomic loss of the transcriptional kinase occurs in ~6% of metastatic castration-resistant prostate cancers (mCRPC) and correlates with poor patient outcomes. Prior studies demonstrate that acute CDK12 loss confers a homologous recombination (HR) deficiency (HRd) phenotype via premature intronic polyadenylation (IPA) of key HR pathway genes, including However, mCRPC patients have not demonstrated benefit from therapies that exploit HRd such as inhibitors of polyADP ribose polymerase (PARP). Based on this discordance, we sought to test the hypothesis that an HRd phenotype is primarily a consequence of acute loss and the effect is greatly diminished in prostate cancers adapted to loss.

View Article and Find Full Text PDF

Unfortunately, ovarian cancer is still diagnosed most often only in an advanced stage and is also the most lethal gynecological cancer. Another problem is the fact that treated patients have a high risk of disease recurrence. Moreover, ovarian cancer is very diverse in terms of molecular, histological features and mutations.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!