News - BRCA2 mutation

NCI 9938: M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)

P1, N=66, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025

3 days ago

Trial completion date • Combination therapy • Surgery • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation

irinotecan • berzosertib (M6620)

Aggressive renal cell carcinoma with somatic BRCA2 mutation-an emerging entity? A case report with literature review. (PubMed, Virchows Arch)

This unusual co-expression of the commonly used IHC stains during the workup of RCC could serve as a potential diagnostic pitfall. Although very rare, it is important for pathologists to be aware of this form of RCC due to its aggressive clinical behavior, possibility of a germline mutation, and current therapeutic options for tumors with BRCA2 mutation.

4 days ago

Review • Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • CA9 (Carbonic anhydrase 9) • MME (Membrane Metalloendopeptidase) • PAX8 (Paired box 8)

BRCA2 mutation • CA9 expression

Cisplatin With or Without Veliparib in Treating Patients With Recurrent or Metastatic Triple-Negative and/or BRCA Mutation-Associated Breast Cancer With or Without Brain Metastases (clinicaltrials.gov)

P2, N=333, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

5 days ago

Trial completion date • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • HER-2 negative • BRCA mutation

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

cisplatin • veliparib (ABT-888)

EVER-132-001: Study of Sacituzumab Govitecan in Chinese Patients With Metastatic Triple-negative Breast Cancer Who Received at Least Two Prior Treatments (clinicaltrials.gov)

P2, N=80, Active, not recruiting, Gilead Sciences | Trial completion date: Dec 2024 --> Dec 2025

5 days ago

Trial completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

Trodelvy (sacituzumab govitecan-hziy)

Prognostic implications of ductal carcinoma in situ components in BRCA1/2-positive breast cancer: a retrospective cohort study. (PubMed, Ann Surg Treat Res)

The presence of a DCIS component carries varied prognostic significance in BRCA1 and BRCA2 mutations. A tailored approach may be necessary when determining treatment options for breast cancer patients with BRCA1/2 mutations based on the presence of DCIS.

5 days ago

Retrospective data • Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA1 mutation + BRCA2 mutation • BRCA1 positive • BRCA2 positive

Next-Generation Sequencing-Guided Treatment of BRCA2-Mutant Metastatic Uterine Leiomyosarcoma With Poly(ADP-ribose) Polymerase Inhibitor Therapy. (PubMed, JCO Precis Oncol)

No abstract available

6 days ago

Journal • Next-generation sequencing • BRCA Biomarker • Metastases

BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation

OptiTROP-Breast01: SKB264 Injection Vs Investigator Selected Regimens to Treat Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer (clinicaltrials.gov)

P3, N=254, Active, not recruiting, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Trial completion date: Dec 2024 --> Mar 2025

6 days ago

Trial completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • HER-2 negative • HER-2 expression • PGR negative • HER-2 negative + HR positive + BRCA mutation

gemcitabine • capecitabine • Halaven (eribulin mesylate) • vinorelbine tartrate • sacituzumab tirumotecan (MK-2870)

Response to Carboplatin and Paclitaxel in the treatment of hereditary breast ovarian cancer syndrome (HBOC): a case report. (PubMed, J Pak Med Assoc)

This dynamic treatment not only led to nearly complete remission of high-grade ovarian serous cancer but also triggered regression in grade-2 invasive ductal breast cancer after just a few rounds of chemotherapy. Consequently, what started as palliative care evolved into a curative triumph.

7 days ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK1 mutation • CHEK1 expression

carboplatin • paclitaxel

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)

P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

9 days ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)

BRCA2 mutation • BRCA1 mutation • ATM mutation

Talzenna (talazoparib)

Research progress on pathogenic germline mutations in malignant tumors (PubMed, Zhonghua Yi Xue Yi Chuan Xue Za Zhi)

With the development of next-generation sequencing technology, more and more germline gene mutations have been discovered recently, which is of great significance for the prevention, screening, and treatment of tumors. This article has provided a review for common germline mutations, detection methods, and advances in drug therapy.

9 days ago

Review • Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • PMS1 (PMS1 protein homolog 1)

TP53 mutation • BRCA2 mutation • BRCA1 mutation

Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002) (clinicaltrials.gov)

P2, N=390, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

9 days ago

Enrollment closed • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • PGR positive • BRCA mutation

Lynparza (olaparib)

11d

Molecular testing of gastrointestinal tumours - current status and future prospects. (PubMed, Rozhl Chir)

In gallbladder and biliary tract cancers, we are mainly looking for IDH1 and IDH2 mutations, FGFR2 gene fusions and mutations, HER2 amplifications or mutations, as well as mutations of BRAF or BRCA1/2. All results should be discussed within the molecular tumor board.

11 days ago

Review • Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

PD-L1 expression • BRCA2 mutation • BRCA1 mutation • BRAF mutation • HER-2 amplification • NRAS mutation • HER-2 expression • IDH2 mutation • FGFR2 mutation • FGFR2 fusion • HER-2 amplification + PD-L1 expression

11d

BRCA1 & BRCA2 methylation as a prognostic and predictive biomarker in cancer: Implementation in liquid biopsy in the era of precision medicine. (PubMed, Clin Epigenetics)

We believe that BRCA1/2 methylation alone or combined with other biomarkers in a clinical setting is expected to change the scenery in prognosis and predicting treatment response in multiple cancer types and is worthy of further attention. The quantitative BRCA1 promoter methylation assessment might predict treatment response in PARPi and analysis of BRCA1/2 methylation in liquid biopsy might define patient subgroups at different time points that may benefit from PARPi. Finally, we suggest a pipeline that could be implemented in liquid biopsy to aid precision pharmacotherapy in BRCA-associated tumors.

11 days ago

Review • Journal • Liquid biopsy • BRCA Biomarker • PARP Biomarker • Biopsy

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA1 promoter methylation

12d

Recent and Future Developments in the Use of Poly (ADP-ribose) Polymerase Inhibitors for Prostate Cancer. (PubMed, Eur Urol Oncol)

PARPi are active against PCa with HRR mutations, especially in those with germline or somatic BRCA1/2 mutations. There is still a need to further optimize patient stratification strategies, particularly for combination approaches. Future research should focus on refining predictive biomarkers, improving treatment delivery strategies, and exploring the potential benefits of PARPi in earlier stages of the disease.

12 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)

BRCA2 mutation • BRCA1 mutation

Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib)

13d

TUBA: Early Salpingectomy (Tubectomy) With Delayed Oophorectomy in BRCA1/2 Gene Mutation Carriers (clinicaltrials.gov)

P=N/A, N=510, Active, not recruiting, University Medical Center Nijmegen | Trial primary completion date: Jan 2025 --> Jan 2030

13 days ago

Trial primary completion date • HEOR

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

14d

Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer (clinicaltrials.gov)

P1/2, N=50, Recruiting, Xing Xie | Trial primary completion date: Jan 2024 --> Dec 2024

14 days ago

Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MUC16 (Mucin 16, Cell Surface Associated)

BRCA2 mutation • BRCA1 mutation • MUC16 elevation

AiRuiYi (fluzoparib) • arsenic trioxide

15d

A scoping review of parents' disclosure of BRCA1/2 genetic alteration test results to underage children. (PubMed, Patient Educ Couns)

These findings equip healthcare professionals in their efforts to develop and test interventions which support the communication of genetic risk information. Furthermore, it is evident there is a need for more research to understand how the disclosure process occurs in the families.

15 days ago

Review • Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

15d

Enhancing PARP inhibitor efficacy using reduction-responsive nanoparticles encapsulating NADP. (PubMed, J Mater Chem B)

The combined effects of elevated NADP+ levels and olaparib synergistically suppress tumor cell growth. Overall, our study offers a promising strategy for the clinical application of NADP+.

15 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

Lynparza (olaparib)

16d

The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models. (PubMed, Basic Res Cardiol)

It gives an overview of preclinical models of breast cancer, such as genetically engineered mouse models, syngeneic murine models, humanized mouse models, and various in vitro and ex vivo systems and models to study cardiovascular side effects of breast cancer therapies. Understanding the underlying mechanism of cardiotoxicity and developing cardioprotective strategies in preclinical models are essential for improving treatment outcomes and reducing long-term cardiovascular risks in breast cancer patients.

16 days ago

Preclinical • Review • Journal • BRCA Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA1 mutation + BRCA2 mutation

17d

Assessment of plasma resolvin levels in women with breast cancer and their associations with disease presentation and immunohistochemical characteristics. (PubMed, Lipids Health Dis)

This is the first human study profiling specific plasma resolvin levels in BC patients, which revealed low plasma levels of some resolvins in patients with BRCA1/2 mutations, triple-negative subtypes and high Ki-67 expression, potentially impacting treatment response and prognosis.

17 days ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA mutation

17d

Testing BRCA 1-2 Mutations in Metastatic Prostate Cancer: Results of a Survey of the Italian Association of Medical Oncology. (PubMed, Clin Genitourin Cancer)

BRCA testing in PC still presents several difficulties in clinical practice that can limit access to PARPi treatment. Better implementation of molecular testing to identify BRCA-mutated patients is crucial for tailored treatment in mCRPC.

17 days ago

Journal • BRCA Biomarker • PARP Biomarker • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA mutation

Lynparza (olaparib)

19d

The incidence of pancreatic cancer in women with a BRCA1 or BRCA2 mutation. (PubMed, Cancer)

The lifetime risk of pancreatic cancer is approximately 2% in women with a BRCA1 mutation and 3% for women with a BRCA2 mutation. The poor survival in hereditary pancreatic cancer underscores the need for novel antitumoral strategies.

19 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • BRCA1 mutation + BRCA2 mutation

19d

RAD51 recruitment but not replication fork stability associates with PARP inhibitor response in ovarian cancer patient-derived xenograft models. (PubMed, NAR Cancer)

Targeted panel sequencing in olaparib-sensitive models lacking BRCA1/2 alterations revealed a MUS81 variant as a possible mechanism underlying PARPi sensitivity. Combined, we show that ex vivo RAD51 analysis effectively predicts in vivo olaparib response and revealed a subset of PARPi-sensitive, HR-deficient ovarian cancer PDX models, lacking a BRCA1/2 alteration.

19 days ago

Preclinical • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • MUS81 (MUS81 Structure-Specific Endonuclease Subunit)

BRCA2 mutation • BRCA1 mutation

Lynparza (olaparib)

20d

Assessing the impact of contraceptive use on reproductive cancer risk among women of reproductive age-a systematic review. (PubMed, Front Glob Womens Health)

Further research is needed to explore contraceptive impacts across different genetic profiles and dosing regimens. https://www.crd.york.ac.uk/prospero/, Prospero (CRD42022332647).

20 days ago

Review • Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

20d

Discovery of a potent PARP1 PROTAC as a chemosensitizer for the treatment of colorectal cancer. (PubMed, Eur J Med Chem)

Furthermore, C6 significantly increased the cytotoxic efficacy of SN-38, an active metabolite of Irinotecan, in BRCA-mutated CRC cells, achieving a favorable combination index (CI) of 0.487. In conclusion, this research underscores the potential benefits of employing a combination therapy that utilizes PAPRP1 degrader C6 alongside Irinotecan for CRC patients harboring BRCA mutations in CRC.

20 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)

BRCA2 mutation • BRCA1 mutation • BRCA mutation

irinotecan

21d

Familial Pancreatic Cancer Research: Bridging Gaps in Basic Research and Clinical Application. (PubMed, Biomolecules)

It highlights the role of homologous recombination (HR) and its therapeutic exploitation via synthetic lethality with PARP inhibitors in BRCA1/2-deficient tumors. The review discusses various pre-clinical models of FPC, including conventional two-dimensional (2D) cell lines, patient-derived organoids (PDOs), patient-derived xenografts (PDXs), and genetically engineered mouse models (GEMMs), as well as new advancements in FPC research.

21 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • BRCA1 mutation + BRCA2 mutation

21d

Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging in Magnetic Resonance in the Assessment of Peritoneal Recurrence of Ovarian Cancer in Patients with or Without BRCA Mutation. (PubMed, Cancers (Basel))

Our study revealed a statistically significant correlation between DWI and DCE parameters in examinations of peritoneal metastasis in patients with BRCA1/2 mutations. Adding DCE perfusion to the MRI protocol for ovarian cancer recurrence in patients with BRCAmut may be a valuable tool.

21 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA wild-type • BRCA mutation

22d

Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer. (PubMed, Curr Oncol)

Furthermore, the use of poly-adenosine diphosphate-ribose polymerase inhibitors in patients with hereditary GC is considered safe and effective. This study provides substantial evidence for guiding the establishment of early treatment for patients with advanced-stage/metastatic GC who harbored BRCA1/2 mutations.

22 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

Lynparza (olaparib) • paclitaxel

22d

The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers. (PubMed, Curr Oncol)

We also emphasize the importance of biomarker identification for personalized management, especially in metastatic settings where treatment intensification is often required. Future research is needed to further elucidate our understanding of the genetics affecting urologic cancers, which will help develop novel, individualized therapies to enhance oncologic outcomes.

22 days ago

Review • Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • PD-L1 overexpression • PTEN mutation

22d

Pattern Anlysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers. (PubMed, Curr Oncol)

The rates of breast/ovarian cancer surveillance, chemoprevention, and risk-reducing surgery were low among unaffected Korean BRCA1/2 mutation carriers. Given this cohort's relatively high risk of developing breast cancer, strategies to encourage active participation in risk reduction are needed.

22 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

22d

Clinical Outcomes of Poly(ADP-Ribose) Polymerase Inhibitors as Maintenance Therapy in Patients with Ovarian Cancer in the Southeastern Region of Korea. (PubMed, Curr Oncol)

In a real-world setting, PARP inhibitors showed efficacy comparable to that reported in published randomized controlled trials and had acceptable safety profiles.

22 days ago

Clinical data • Retrospective data • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

Lynparza (olaparib) • Zejula (niraparib)

27d

Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer (clinicaltrials.gov)

P1, N=44, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Apr 2017 --> Sep 2024

27 days ago

Trial primary completion date • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • HER-2 negative • PGR positive • HER-2 negative + PGR positive

carboplatin • veliparib (ABT-888)

27d

Olaparib monotherapy in advanced triple-negative breast cancer patients with homologous recombination deficiency and without germline mutations in BRCA1/2: The NOBROLA phase 2 study. (PubMed, Breast)

The observed results could prompt further investigation.

27 days ago

Clinical • P2 data • Journal • BRCA Biomarker • PARP Biomarker • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)

BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation

Lynparza (olaparib)

27d

SART1 modulates poly-(ADP-ribose) chain accumulation and PARP1 chromatin localization. (PubMed, iScience)

Silencing of SART1 leads to an increased sensitivity of cells to DNA damage induced by IR, irrespective of BRCA1 status and to PARPis only in absence of BRCA1. These results suggest that SART1 could be clinically utilized to improve PARPi efficacy.

27 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)

BRCA2 mutation • BRCA1 mutation

28d

Luminal breast epithelial cells of BRCA1 or BRCA2 mutation carriers and noncarriers harbor common breast cancer copy number alterations. (PubMed, Nat Genet)

BRCA1/BRCA2 carriers contained a small percentage of cells with extreme aneuploidy, featuring loss of TP53, BRCA1/BRCA2 LOH and multiple breast cancer-associated CNAs. Our findings suggest that CNAs arising in normal luminal breast epithelium are precursors to clonally expanded tumor genomes.

28 days ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

29d

Anthracyclines-induced cardiotoxicity in patients with early breast cancer carrying germline BRCA1/2 mutation: the BRCAN study. (PubMed, Oncologist)

gBRCA1/2m patients could represent a higher-risk population for AIC. gBRCA1/2 status should be one of the factors to consider in deciding on adjuvant anthracycline necessity. This population could benefit from a cardio-oncology closer follow-up and cardioprotective strategies.

29 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CRP (C-reactive protein)

BRCA2 mutation • BRCA1 mutation

29d

Molecular mechanisms restoring olaparib efficacy through ATR/CHK1 pathway inhibition in olaparib-resistant BRCA1/2MUT ovarian Cancer models. (PubMed, Biochim Biophys Acta Mol Basis Dis)

Olaparib-resistant xenografts were treated with olaparib, ATR inhibitor (ATRi, ceralasertib), CHK1 inhibitor (CHK1i, MK-8776) or their combinations. Our collective findings indicate that ATR/CHK1 pathway inhibition restores the olaparib efficacy in resistant BRCA1/2MUT high-grade serous OC, highlighting promising approach for olaparib rechallenge of non-responsive patients. Uncovered mechanisms might improve our understanding of acquisition and overcoming resistance to olaparib in ovarian cancer.

29 days ago

Preclinical • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • VIM (Vimentin) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

BRCA2 mutation • BRCA1 mutation • VIM expression

Lynparza (olaparib) • ceralasertib (AZD6738) • MK-8776

30d

Olaparib, Durvalumab, and Tremelimumab in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube or Primary Peritoneal Cancer With BRCA1 or BRCA2 Mutation (clinicaltrials.gov)

P2, N=40, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed

30 days ago

Trial completion • Combination therapy

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

Lynparza (olaparib) • Imfinzi (durvalumab) • Imjudo (tremelimumab)

30d

Bibliometric analysis of olaparib and pancreatic cancer from 2009 to 2022: A global perspective. (PubMed, World J Gastrointest Oncol)

Our findings identified trends in olaparib and pancreatic cancer, with China and the USA leading and with global cooperation tightening. O'Reilly EM's team and Memorial Sloan-Kettering had the highest output. The Journal of Clinical Oncology was the most cited journal. More PARP inhibitors are emerging, and combination therapy is suggested for future therapeutic trends.

30 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA mutation

Lynparza (olaparib)

Use of sacituzumab govitecan in frail patients with skin disease. (PubMed, Recenti Prog Med)

The clinical case described concerns a 53-year-old patient with triple-negative disease, metastatic to the skin, fragile, not due to comorbidities, but due to toxicities from previous antiblastic treatments. The patient has no family history of breast cancer and does not have a mutation in the BRCA1/2 genes. In pathological history, only arterial hypertension under medical therapy with nebivolol.

1 month ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation

Trodelvy (sacituzumab govitecan-hziy)

Exactis-03: Combination of Olaparib and Navitoclax in Women with HGSC and TNBC (clinicaltrials.gov)

P1, N=36, Active, not recruiting, Sunnybrook Health Sciences Centre | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2024 --> Mar 2025

1 month ago

Enrollment closed • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • PALB2 mutation

Lynparza (olaparib) • navitoclax (ABT 263)

PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer. (PubMed, Proc Natl Acad Sci U S A)

Regardless of the BRCA/HRD-status, the induction of ssGAPs in preclinical models of ovarian cancer cells correlates with PARGi sensitivity. Patient-derived organoids (PDOs) may be a useful model system for testing PARGi sensitivity and functional biomarkers.

1 month ago

Preclinical • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • HRD • BRCA mutation • PARP1 mutation