Somatic and germline aberrations in homologous recombination repair genes among Chinese high-risk breast cancer patients by multi-gene next-generation sequencing DOI
Ling Ling Xie, Jie Chen,

YanYing Zheng

et al.

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Language: Английский

The Landscape of PARP Inhibitors in Solid Cancers DOI Open Access

Marta Muzzana,

Massimo Broggini, Giovanna Damia

et al.

OncoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 18, P. 297 - 317

Published: March 1, 2025

PARP inhibitors are a class of agents that have shown significant preclinical activity in models defective homologous recombination (HR). The identification synthetic lethality between HR defects and inhibition led to several clinical trials tumors with known (initially mutations BRCA1/2 genes subsequently other involved HR). These studies demonstrated responses breast ovarian cancers, which proportion patients defects. Since the approval first inhibitor (PARPi), olaparib, been developed, expanding armamentarium available clinicians this setting. positive results obtained cancer expanded use PARPi solid defects, including prostate pancreatic these identified. now also for subset This review summarizes their potential when combined agents, immune checkpoint likely further increase survival still needs dramatic improvement.

Language: Английский

Citations

1
Poly (adenosine diphosphate‐ribose) polymerase inhibitors in the treatment of triple‐negative breast cancer with homologous repair deficiency DOI Creative Commons

Peng Yuan,

Nan Ma, Binghe Xu

et al.

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(6), P. 2774 - 2792

Published: June 24, 2024

Breast cancer (BC) is a highly heterogeneous disease, and the presence of germline breast gene mutation (gBRCAm) associated with poor prognosis. Triple-negative (TNBC) BC subtype, characterized by absence hormone growth factor receptor expression, making therapeutic decisions difficult. Defects in DNA damage response pathway due to genes (BRCA 1/2) lead homologous recombination deficiency (HRD). However, HRD conditions, poly (adenosine diphosphate-ribose) polymerase (PARP) proteins repair tumor cell survival. Biological understanding leads development PARP inhibitors (PARPi), which trap cause genomic instability lysis. assessment can be an important biomarker identifying gBRCAm patients who could benefit from PARPi therapy. identified (HRR) gene-based assays, genomic-scarring assays mutational signatures, transcription protein expression profiles, functional assays. gold standard methodologies that are robust reliable assess not available currently. Hence, there pressing need develop accurate biomarkers tumors guide targeted therapies such as BC. has shown fruitful outcomes chemotherapy studies preliminary evidence on intervention monotherapy combination therapy HRD-stratified patients. Furthermore, ongoing trials exploring potential clinically complex TNBC settings, where testing used adjunct stratify based BRCA mutations.

Language: Английский

Citations

6
Screening and Testing for Homologous Recombination Repair Deficiency (HRD) in Breast Cancer: an Overview of the Current Global Landscape DOI Creative Commons
Gordon R. Daly,

Sindhuja Naidoo,

Mohammad Alabdulrahman

et al.

Current Oncology Reports, Journal Year: 2024, Volume and Issue: 26(8), P. 890 - 903

Published: June 1, 2024

Abstract Purpose of Review Homologous recombination repair deficiency (HRD) increases breast cancer susceptibility and influences both prophylactic active management cancer. This review evaluates HRD testing the therapeutic implications in a global context. Recent Findings Ongoing research efforts have highlighted importance beyond BRCA1/2 as potential target However, despite improved affordability next-generation sequencing (NGS) discovery PARP inhibitors, economic geographical barriers access to screening do not allow all patients benefit from personalized treatment approach they provide. Summary Advancements modalities targeted therapeutics enable tailored management. inequalities optimized treatments are contributing widening health disparities globally.

Language: Английский

Citations

4
Substitutions at the C-8 position of quinazolin-4-ones improve the potency of nicotinamide site binding tankyrase inhibitors DOI Creative Commons
Chiara Bosetti, Dionysis Kampasis,

Shoshy Alam Brinch

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 288, P. 117397 - 117397

Published: Feb. 15, 2025

Language: Английский

Citations

0
Novel Strategies in Breast Cancer Management: from Treatment to Long-term Remission DOI

S Habibi,

Shabbou Bahramian,

Saeedeh Zare Jalise

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104715 - 104715

Published: April 1, 2025

Language: Английский

Citations

0
PARP Inhibitors in the Neoadjuvant Setting; A Comprehensive Overview of the Rationale for their Use, Past and Ongoing Clinical Trials DOI Creative Commons

Minatoullah Habaka,

Gordon R. Daly,

Deborah Shinyanbola

et al.

Current Oncology Reports, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Abstract Purposeof Review Poly (ADP-ribose) polymerases (PARPs) are enzymes essential for detecting and repairing DNA damage through poly-ADP-ribosylation. In cancer, cells with deficiencies in homologous recombination repair mechanisms often become more dependent on PARP-mediated to effectively dsDNA breaks. As such, PARP inhibitors (PARPis) were introduced into clinical practice, serving as a key targeted therapy option synthetic lethality the treatment of cancers deficiency (HRD). Though PARPis currently approved adjuvant setting several cancer types such ovarian, breast, prostate pancreatic their potential role neoadjuvant remains under investigation. This review outlines rationale using PARPi evaluates findings from early ongoing trials. Recent Findings Our analysis indicates that numerous studies have explored HRD-related cancers. The majority trials been performed breast ovarian while phase II/III evidence supporting efficacy limited. Summary Studies investigating Future research should prioritize combination strategies immune checkpoint expand outcome measures include patient satisfaction quality-of-life metrics.

Language: Английский

Citations

0
Immunotherapeutic effects of de novo benzimidazole derivative and prebiotic bacterial levan against triple-negative breast tumors by harnessing the immune landscape to intercept the oncogenic transcriptome DOI
Heba Shawky, Dalia B. Fayed, Somaia S. Abd El‐Karim

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 289, P. 138844 - 138844

Published: Dec. 18, 2024

Language: Английский

Citations

1
Effect of Eight Weeks of Resistance Training on Fatigue, Quality of Life, and Body Composition of Metastatic Breast Cancer Patients: A Clinical Trial DOI
Somayeh Nazari,

N Behpour,

Behrooz Gharib

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 17(1), P. 4 - 21

Published: March 1, 2024

Language: Английский

Citations

0
Substitutions at the C-8 position of quinazolin-4-ones improve the potency of nicotinamide site binding tankyrase inhibitors DOI Creative Commons
Chiara Bosetti,

Dionisis Kampasis,

Albert Galera‐Prat

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

Abstract Human diphtheria toxin-like ADP-ribosyltransferases, PARPs and tankyrases, transfer ADP-ribosyl groups to other macromolecules, thereby controlling various signaling events in cells. They are considered promising drug targets, especially oncology, some small molecule inhibitors have already been developed. These typically interact with the nicotinamide binding site extend along NAD + groove of catalytic domain. Quinazolin-4-ones explored as scaffolds for such we identified a new position within domain that has not extensively studied yet. In this study, investigate larger substituents at C-8 and, using X-ray crystallography, demonstrate nitro- diol-substituents engage interactions TNKS2, improving both affinity selectivity. Both exhibit intriguing inhibition compound 49 displaying an IC 50 65 nM, while 40 ’s value is 14 nM. analogues show efficacy cell assays attenuate tankyrase-controlled Wnt/β-catenin sub-micromolar . When tested against wider panel enzymes, displayed high selectivity towards whereas also inhibited PARPs. The results offer insights inhibitor development targeting tankyrases by focusing on subsite between mobile active loop canonical site.

Language: Английский

Citations

0
Somatic and germline aberrations in homologous recombination repair genes among Chinese high-risk breast cancer patients by multi-gene next-generation sequencing DOI
Ling Ling Xie, Jie Chen,

YanYing Zheng

et al.

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Language: Английский

Citations

0