News - BRCA mutation - LARVOL VERI

18h

Morphologic Characteristics Seen in High-grade Serous Ovarian Carcinoma Metastases in Postneoadjuvant Chemotherapy Resections. (PubMed, Int J Gynecol Pathol)

When compared with the pretreatment biopsies of metastases taken at the time of diagnosis, the postneoadjuvant, treated metastases had unique morphologic findings, such as cytoplasmic vacuolization, cellular enlargement with eosinophilic cytoplasm, macro-nucleoli, cellular discohesion, and micropapillary architecture with abundant psammoma bodies. Metastases were also morphologically different from the primary site in the postneoadjuvant resection specimens.

18 hours ago

Journal • BRCA Biomarker

BRCA (Breast cancer early onset)

BRCA mutation

The role of ATP6V0D2 in breast cancer: associations with prognosis, immune characteristics, and TNBC progression. (PubMed, Front Oncol)

Furthermore, ATP6V0D2 knockdown inhibited TNBC cells invasion, migration, and proliferation abilities. ATP6V0D2 acts as a promising indicator for both diagnosis and prediction of outcomes in breast cancer and could potentially be a novel therapeutic target for BRCA.

2 days ago

Journal • BRCA Biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CD8 (cluster of differentiation 8) • BRCA (Breast cancer early onset)

PIK3CA mutation • BRCA mutation

Advancements in Clinical Research and Emerging Therapies for Triple-Negative Breast Cancer Treatment. (PubMed, Eur J Pharmacol)

We delve into the specifics of PARPi, androgen receptor (AR) inhibitors, Cancer stem cells (CSCs), PI3K/ Protein Kinase B (AKT)/ mammalian target of rapamycin (mTOR), the transforming growth factor-beta (TGF-β), Ntoch, Wnt/β-catenin, hedgehog (Hh) pathway inhibitors, Epigenetic target-mediated drug delivery, ADCs, immune checkpoint inhibitors (ICIs)and novel immunotherapeutic solutions, contextualizing TNBC within current treatment paradigms. By elucidating the mechanisms of these drugs and their prospective clinical applications, we aim to shed light on the challenges and underscore the beacon of hope that translational research and innovative therapies represent for the oncology field.

3 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • mTOR (Mechanistic target of rapamycin kinase) • BRCA (Breast cancer early onset) • TGFB1 (Transforming Growth Factor Beta 1)

HR positive • HER-2 expression • BRCA mutation

Molecular pathology of gastrointestinal neoplasms (PubMed, Magy Onkol)

The responsiveness of gastrointestinal stromal tumors to imatinib requires validation via molecular testing. Patients diagnosed with pancreatic cancer may see enhanced survival rates by targeted therapy addressing microsatellite instability and BRCA mutations. In bile duct malignancies, especially intrahepatic cholangiocarcinoma of the small duct variant, the analysis of IDH1 mutations and FGFR2 fusions presents new treatment prospects.

3 days ago

Review • Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CLDN18 (Claudin 18) • BRCA (Breast cancer early onset)

KRAS mutation • BRAF mutation • HER-2 amplification • NRAS mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • BRCA mutation • IDH1 mutation + FGFR2 fusion

imatinib

Haematologic outcomes and associated clinical characteristics among patients receiving Olaparib therapy in the UAE: a retrospective chart review. (PubMed, Ann Med)

Our findings highlight the side effects of Olaparib therapy in terms of haematology which could be avoided. Further studies are needed to better understand the therapeutic management of Olaparib and the mitigation of haematologic complications.

4 days ago

Retrospective data • Review • Journal • BRCA Biomarker • PARP Biomarker

BRCA (Breast cancer early onset)

BRCA mutation

Lynparza (olaparib)

Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin-expressing cancers. (PubMed, Sci Adv)

The P-selectin-targeted nanoparticles showed enhanced accumulation in 3D spheroids and tissues of P-selectin-expressing BRAF-mutated melanomas and BRCA-mutated breast cancers, resulting in superior in vivo efficacy and safety. This nanoplatform could advance the codelivery of a plethora of anticancer drug combinations to various P-selectin-expressing tumors.

5 days ago

Journal • BRCA Biomarker

BRAF (B-raf proto-oncogene) • BRCA (Breast cancer early onset)

BRAF mutation • BRCA 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

6 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)

IJB-BRCAPreg-CE2630: Safety of Pregnancy in BRCA Mutated Breast Cancer Patients (clinicaltrials.gov)

P=N/A, N=4732, Completed, Jules Bordet Institute | Active, not recruiting --> Completed | N=2200 --> 4732

6 days ago

Trial completion • Enrollment change

BRCA (Breast cancer early onset)

BRCA mutation

Olaparib as Treatment Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer: Phase III SOLO3 Study Final Overall Survival Results. (PubMed, J Clin Oncol)

Two hundred sixty-six patients were randomly assigned 2:1 to olaparib tablets (300 mg twice daily; n = 178) or physician's choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88). BRCA reversion mutations might have contributed to this finding. No patient randomly assigned to olaparib with a BRCA reversion mutation detected at baseline (6 of 170 [3.5%]) achieved an objective tumor response.

6 days ago

P3 data • Journal • BRCA Biomarker • PARP Biomarker

BRCA (Breast cancer early onset)

BRCA mutation

Lynparza (olaparib) • gemcitabine • paclitaxel • pegylated liposomal doxorubicin • topotecan

Bioinformatics insights into the role of GFPT1 in breast invasive carcinoma: implications for tumor prognosis, immune modulation, and therapeutic applications. (PubMed, Front Genet)

These findings indicate that GFPT1 is a novel prognostic biomarker and a predictive indicator of chemotherapy response in invasive breast carcinoma. GFPT1 influences mRNA translation, cell cycle regulation, and M2 macrophage infiltration, thereby promoting cancer cell proliferation and metastasis.

6 days ago

Journal • Tumor mutational burden • BRCA Biomarker

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA (Breast cancer early onset)

TP53 mutation • TMB-H • BRCA mutation

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

A Study for Post-Marketing Surveillance of Niraparib in the Treatment of Adult Participants for Approved Indications in South Korea (clinicaltrials.gov)

P=N/A, N=662, Completed, Takeda | Recruiting --> Completed

8 days ago

Trial completion

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

HRD • BRCA mutation

Zejula (niraparib)

IIT2015-18-Mita-MK3475: Pembrolizumab in Combination with Olaparib in Advanced BRCA-mutated or HDR-defect Breast Cancer (clinicaltrials.gov)

P2, N=20, Active, not recruiting, Yuan Yuan | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2026 --> Oct 2024

8 days ago

Enrollment closed • Trial primary completion date • Combination therapy • Checkpoint inhibition • IO biomarker • Metastases

BRCA (Breast cancer early onset) • CDK6 (Cyclin-dependent kinase 6)

HER-2 positive • HR positive • BRCA mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)

10d

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

10 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

12d

Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With BRCA Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy. (PubMed, JCO Precis Oncol)

In real-world setting, substantially lower OS in mCRPC is observed for BRCA- and PTEN/TP53/RB1-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for BRCA patients.

12 days ago

Journal • BRCA Biomarker • Metastases

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • BRCA (Breast cancer early onset)

TP53 mutation • PTEN mutation • RB1 mutation • BRCA mutation

12d

Combating tumor PARP inhibitor resistance: Combination treatments, nanotechnology, and other potential strategies. (PubMed, Int J Pharm)

Subsequently, this paper presents several promising strategies to tackle PARPi resistance, including but not limited to: structural modifications of PARPi, deployment of gene editing systems, implementation of "membrane lipid therapy," and modulation of cellular metabolism in tumors. By integrating these strategies, this research will provide comprehensive approaches to overcome the resistance of PARPi in cancer treatment and offer guidance for future research and clinical practice.

12 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

BRCA (Breast cancer early onset) • DRD (DNA Repair Deficiency)

DDR • BRCA mutation

14d

New Therapeutic Options for BRCA Mutant Patients. (PubMed, Annu Rev Med)

An understanding of the biology of BRCA1 and BRCA2 led to the development of targeted therapeutics, specifically poly(ADP-ribose) polymerase (PARP) inhibitors, which are approved by the US Food and Drug Administration for multiple BRCA1/2-associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical BRCA1/2 tumors, and we describe novel agents under study.

14 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker

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

BRCA mutation

15d

Synthetic lethal strategies for the development of cancer therapeutics. (PubMed, Nat Rev Clin Oncol)

Spurred by the clinical success of PARP inhibitors in patients with BRCA-mutant cancers, novel agents targeting multiple synthetic lethal interactions within DNA damage response pathways are in clinical development, and rational strategies targeting synthetic lethal interactions spanning alterations in epigenetic, metabolic and proliferative pathways have also emerged and are in late preclinical and/or early clinical testing. In this Review, we provide a comprehensive overview of established and emerging technologies for synthetic lethal drug discovery and development and discuss promising therapeutic strategies targeting such interactions.

15 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker • Synthetic lethality

BRCA (Breast cancer early onset)

BRCA 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

Homologous recombination deficiency testing in patients with high grade ovarian cancer: factors influencing test success. (PubMed, Future Oncol)

97% of patients with HRD-positive tumors treated at the center received a PARP inhibitor as part of their first-line maintenance treatment. By optimizing the factors affecting HRD test success, we can obtain faster results and offer patients appropriate treatment at earlier time points to improve patient outcomes.

19 days ago

Journal • BRCA Biomarker • PARP Biomarker

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

HRD • BRCA 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

21d

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.

21 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

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)

21d

Serous Tubal Intraepithelial Carcinoma (STIC): A Review of the Literature on the Incidence at the Time of Prophylactic Surgery. (PubMed, Diagnostics (Basel))

The etiopathogenesis of STIC involves complex interactions between genetic, environmental, and molecular factors. Further research is needed to fully understand its mechanisms and identify additional risk factors beyond BRCA mutations. Establishing a national database of STIC cases could facilitate future research and improve patient outcomes.

21 days ago

Review • Journal • BRCA Biomarker • Surgery

TP53 (Tumor protein P53) • BRCA (Breast cancer early onset)

TP53 mutation • BRCA mutation

24d

A pan-cancer analysis of the oncogenic function of HMGB1 in human tumors. (PubMed, Biochem Biophys Rep)

Additionally, we discovered that the frequency of HMGB1 mutations ranked among the top 20 mutated genes in the 95 patients' data, indicating that HMGB1 plays an important role in the development and prognosis of various solid tumors. This pan-cancer study of HMGB1 underscores its potential as a signature marker and target for the management of various tumor types.

24 days ago

Journal • BRCA Biomarker • Pan tumor

BRCA (Breast cancer early onset) • HMGB1 (High Mobility Group Box 1)

BRCA mutation

24d

Current practices for the management of advanced high-grade epithelial ovarian cancer in the UK: OC-NOW survey (2023). (PubMed, Future Oncol)

All respondents agreed that cytoreductive surgery should be considered at first recurrence, and 65% recommended using the Descriptive Evaluation of Preoperative Selection Criteria for Operability in Recurrent Ovarian Cancer (DESKTOP) III criteria to guide secondary cytoreduction. Platinum responders typically receive poly (ADP-ribose) polymerase inhibitor maintenance therapy, regardless of HRD status. Respondents reinforce that most primary OC patients in the UK have known HRD and BRCA mutation status, and the role of secondary cytoreduction is increasingly recognized.

24 days ago

Journal • BRCA Biomarker • Metastases

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

HRD • BRCA mutation

25d

Medicaid Coverage of NCCN- and ASCO/SSO-Guideline-Concordant BRCA Germline Testing for Patients with Breast Cancer: Opportunity to Embrace Rapid Advancements in Precision Medicine. (PubMed, Ann Surg Oncol)

Significant variation in Medicaid coverage for BRCA germline mutation testing may inadvertently exclude socially and economically marginalized populations from the emerging standard of care. Policy language should consider explicit mention of coverage in accordance with NCCN guidelines.

25 days ago

Reimbursement • US reimbursement • Journal • Medicaid • BRCA Biomarker • Discordant

BRCA (Breast cancer early onset)

BRCA mutation

26d

Elucidating acquired PARP inhibitor resistance in advanced prostate cancer. (PubMed, Cancer Cell)

For BRCA2 HomDels, selection for rare subclones without BRCA2-HomDel is observed following PARPi, confirmed by single circulating-tumor-cell genomics, biopsy fluorescence in situ hybridization (FISH), and RNAish. These data support the need for restored HRR function in PARPi resistance.

26 days ago

Journal • BRCA Biomarker • PARP Biomarker • Metastases

BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)

PALB2 mutation • BRCA mutation

27d

Veliparib With or Without Carboplatin in Treating Patients With Stage III or IV Breast Cancer (clinicaltrials.gov)

P2, N=74, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Sep 2024 | Trial primary completion date: Jun 2025 --> Sep 2024

27 days ago

Trial completion • Trial completion date • Trial primary completion date • Combination therapy • Metastases

BRCA (Breast cancer early onset)

BRCA mutation

carboplatin • veliparib (ABT-888)

27d

Combination strategies with PARP inhibitors in BRCA-mutated triple-negative breast cancer: overcoming resistance mechanisms. (PubMed, Oncogene)

The review also discusses the evolving role of PARPis within the broader treatment paradigm for BRCA-mutated TNBC, emphasising the need for ongoing research and clinical trials to optimise combination strategies. By tackling the challenges associated with PARPi resistance and exploring novel combination therapies, this review sheds light on the future possibilities for improving outcomes for patients with BRCA-mutated TNBC.

27 days ago

Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

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

BRCA mutation

28d

NXP800-101: A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer (clinicaltrials.gov)

P1, N=61, Recruiting, Nuvectis Pharma, Inc. | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> May 2025

28 days ago

Trial completion date • Trial primary completion date • Metastases

ARID1A (AT-rich interaction domain 1A) • BRCA (Breast cancer early onset)

ARID1A mutation • BRCA mutation

NXP800

30d

Galinpepimut-S in Combination With Pembrolizumab in Patients With Selected Advanced Cancers (clinicaltrials.gov)

P1/2, N=26, Completed, Sellas Life Sciences Group | Active, not recruiting --> Completed | N=90 --> 26

30 days ago

Trial completion • Enrollment change • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PGR (Progesterone receptor) • WT1 (WT1 Transcription Factor) • BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated)

HER-2 negative • KRAS wild-type • RAS wild-type • BRCA mutation • PGR negative

Keytruda (pembrolizumab) • Zeltherva (galinpepimut-S) • Leukine (sargramostim)

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)

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

Real-World Clinical Outcomes of Treatment With Olaparib for BRCA1/2 Mutation-Positive Metastatic Breast Cancer in Japanese Patients. (PubMed, Cureus)

Our data showed that olaparib is effective in the real world. The incidence of neutropenia seemed higher in Japanese patients.

1 month ago

Clinical data • Journal • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world • Metastases

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 • BRCA mutation

Lynparza (olaparib)

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 month ago

Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

Triple negative breast cancer: Current status and perspectives (PubMed, Bull Cancer)

Dose-dense chemotherapy regimens and the addition of carboplatin have been associated with an improvement in these response rates. Furthermore, immunotherapy, particularly pembrolizumab, has shown significant benefits in terms of recurrence-free survival...In conclusion, despite recent progress, TNBC remains a major clinical challenge. A better understanding of its biology and a personalized therapeutic approach are essential to improve clinical outcomes for patients with this aggressive form of breast cancer.

1 month ago

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

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA (Breast cancer early onset)

HER-2 overexpression • BRCA mutation

Keytruda (pembrolizumab) • carboplatin