News - BRCA1 mutation

Long-Term Breast Cancer Risk in Hodgkin Lymphoma Survivors: Evaluating Background Parenchymal Enhancement and Radiotherapy-Induced Toxicity. (PubMed, Cancers (Basel))

The study highlights the long-term risk of BC in HL survivors and suggests that advanced RT techniques and targeted therapies may help reduce the incidence of secondary tumors. Future research should focus on understanding the genetic and biological mechanisms behind treatment-induced cancers.

1 day ago

Journal • BRCA Biomarker

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

BRCA2 mutation • BRCA1 mutation • BRCA1 mutation + BRCA2 mutation

The Tumour Microenvironment and Epigenetic Regulation in BRCA1 Pathogenic Variant-Associated Breast Cancers. (PubMed, Cancers (Basel))

While LSD-1 itself does not directly cause mutations in BRCA1 or BRCA2 genes, its epigenetic influence sheds light on the potential role of LSD-1 inhibitors as a therapeutic approach in managing breast cancer, particularly in individuals with BRCA1/2 PVs. Targeting LSD-1 may help counteract its detrimental effects and provide a promising avenue for therapy in this specific subgroup of breast cancer.

1 day ago

Review • Journal • BRCA Biomarker

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

BRCA2 mutation • BRCA1 mutation • BRCA1 expression

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)

Proline variants in the BRCA1 coiled-coil domain disrupt folding and binding to PALB2. (PubMed, Protein Sci)

Structural analysis indicates that all BRCA1 mutations to proline tested disrupt α-helix formation and therefore are not well tolerated even when located at positions outside of the PALB2-binding interface. This assay and the structural hypothesis described will be helpful for assessing risk for variants identified in the future in the BRCA1/PALB2 interaction domains.

4 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2)

BRCA1 mutation • PALB2 mutation

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)

Integrated immunogenomic analyses of high-grade serous ovarian cancer reveal vulnerability to combination immunotherapy. (PubMed, Front Immunol)

Genomic instability in HGSOC affects the tumor immune environment, and TAMs play a crucial role in modulating the immune response. Based on various datasets, we have developed a diagnostic application that uses RNA sequencing data not only to comprehensively characterize HGSOC but also to predict vulnerability and response to combination immunotherapy.

5 days ago

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

BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • LILRB4 (Leukocyte Immunoglobulin Like Receptor B4) • TREM2 (Triggering Receptor Expressed On Myeloid Cells 2)

BRCA1 mutation

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

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)

Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)

P2, N=20, Recruiting, Massachusetts General Hospital | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

6 days ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • XRCC2 (X-Ray Repair Cross Complementing 2) • RAD54B (RAD54 Homolog B) • XRCC3 (X-Ray Repair Cross Complementing 3)

BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation • HRD signature

Zejula (niraparib)

Integration of Ayurvedic and Allopathic treatment in hereditary breast and ovarian cancer patient with Germline BRCA1 mutation for long term disease free survival: A case report. (PubMed, J Ayurveda Integr Med)

Methotrexate and Inj. Carboplatin from June to August 2004 followed by optimum cytoreduction in September 2004...Tab Etoposide was given from December 2004 to October 2006...Now she is living with better quality of life with adjunct Ayurvedic treatment, including Oral Ayurvedic Medicines possessing Rasayana (immunomodulatory) and hepato-protective activity and 12 sets of Panchakarma Chikitsa. In this case of Stage IIIA Ovarian carcinoma and second primary Breast carcinoma with BRCA 1 genetic mutation (HBOC syndrome), a long-term 13 years of disease-free survival, and 20 years of overall survival is achieved with the integration of Ayurvedic treatment and conventional cancer treatment.

7 days ago

Journal • BRCA Biomarker

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

BRCA1 mutation • BRCA mutation

carboplatin • etoposide IV • methotrexate

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

Role of BRCA1 in glioblastoma etiology. (PubMed, Cell Oncol (Dordr))

Despite these advances, the heterogeneity of glioblastoma and its complex tumor microenvironment make the translation of such approaches into clinical practice still challenging, and there is an "unmet need". This review discusses the current mechanisms of etiology and potential treatment of BRCA1-related glioblastoma.

8 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog)

BRCA1 mutation • BRCA1 expression

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)

10d

Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma? (PubMed, Arch Pathol Lab Med)

The combination of these 3 criteria showed high specificity (0.99; 95% CI, 0.97-0.99) but low sensitivity (0.07; 95% CI, 0.04-0.10). The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice.

10 days ago

Journal • BRCA Biomarker

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

BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation

Myriad myChoice® CDx Plus

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

15d

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

15 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

16d

Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a BRCA1 mutation. (PubMed, Oncol Lett)

In conclusion, the findings of the present study demonstrated that AZD2281 significantly enhanced FABP4 expression, leading to diminished antitumor efficacy in OC cells with a BRCA mutation by regulating CEBPα-PPARγ. Conversely, the combination of AZD2281 and FABP4 inhibitor BM S309403 demonstrated heightened antitumor effectiveness, presenting a promising therapeutic strategy for treating patients with OC with a BRCA mutation.

16 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA (Breast cancer early onset) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • FABP4 (Fatty Acid Binding Protein 4)

BRCA1 mutation • BRCA mutation

Lynparza (olaparib)

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

Nanoparticulate drug combination inhibits DNA damage repair and PD-L1 expression in BRCA-mutant and wild type triple-negative breast cancer. (PubMed, J Control Release)

The results demonstrate that the iRGD-DOX-oHA-PLNs efficiently downregulated single and double-strand DNA repair proteins and enhanced DNA damage while decreasing PD-L1 expression compared to olaparib. Accordingly, iRGD-DOX-oHA-PLN treatment showed significantly higher efficiency in reducing levels of primary tumor growth and numbers of metastases to the lung and liver compared to olaparib in vitro and in vivo in both BRCA1-mutant and wild type TNBC orthotopic xenograft models.

17 days ago

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

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

PD-L1 expression • BRCA1 mutation • BRCA mutation

Lynparza (olaparib)

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

Incidental Serous Tubal Intraepithelial Carcinoma Finding in a Nepalese Patient Undergoing Opportunistic Salpingectomy and the Discovery of a BRCA1 Pathogenic Variant. (PubMed, O G Open)

Diagnosing STICs in understudied populations could lead to the discovery of an HBOC PV which the patient may not have discovered until after a cancer diagnosis. Identification of a STIC in an average risk patient should lead to a referral for genetic counseling and screening.

20 days ago

Journal • BRCA Biomarker

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

BRCA1 mutation

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

HSP90 buffers deleterious genetic variations in BRCA1. (PubMed, bioRxiv)

We estimate that HSP90 buffers 11% to 28% of known human BRCA1- BRCT missense mutations. Our work extends the clinical significance of HSP90 buffering to a prevalent class of variations in BRCA1 , pioneering its importance in cancer predisposition and therapy resistance.

20 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

BRCA1 mutation

20d

BRCA loss of function including BRCA1 DNA-methylation, but not BRCA-unrelated homologous recombination deficiency, is associated with platinum hypersensitivity in high-grade ovarian cancer. (PubMed, Clin Epigenetics)

In HGOC BRCA mutational status together with BRCA1-methylation exhibit the best predictive power for favorable clinical outcome and thus high sensitivity to platinum-based therapy, whereas BRCA-unrelated HRD positivity was not associated with improved platinum sensitivity.

20 days ago

Journal • BRCA Biomarker • PARP Biomarker • Epigenetic controller

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

BRCA1 mutation • HRD • BRCA wild-type • HRD + BRCA1 mutation • BRCA mutation • BRCA1 expression

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

21d

Poly (ADP-Ribose) Polymerase Inhibitor Olaparib-Resistant BRCA1-Mutant Ovarian Cancer Cells Demonstrate Differential Sensitivity to PARP Inhibitor Rechallenge. (PubMed, Cells)

UWB-OlaJR exhibits varying sensitivity to PARPis, showing cross-resistance to veliparib and talazoparib, and sensitivity with increased cytotoxicity to niraparib and rucaparib. Moreover, S1 nuclease fiber assay shows that niraparib and rucaparib induce greater DNA single-strand gaps than other PARPis, leading to increased DNA damage and cell death. Our study provides novel insights into differential PARPi sensitivity in olaparib-resistant BRCA-mutant OvCa, which requires further investigation of inter-agent differences in large prospective studies.

21 days ago

Journal • BRCA Biomarker • PARP Biomarker

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

BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation

Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib) • veliparib (ABT-888)

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

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

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