News - HRD - LARVOL VERI

22h

Deep multi-omics integration approach reveals new molecular features of uterine leiomyosarcoma. (PubMed, Biochim Biophys Acta Mol Basis Dis)

Interestingly, the expression of Ki67 and CTHRC1 exhibits a strong negative correlation, underscoring two distinct and mutually exclusive biological profiles in uLMS: (i) highly proliferative tumors, characterized by elevated Ki67 expression, and (ii) tumors driven by ECM remodeling, marked by high CTHRC1 levels. Taken together, this deep functional multi-omics approach contributes to the detection of new molecular features of uLMS and suggests that patients could benefit from precision oncology in clinical practice.

22 hours ago

Journal

KRAS (KRAS proto-oncogene GTPase) • HRD (Homologous Recombination Deficiency) • EEF1A1 (Eukaryotic Translation Elongation Factor 1 Alpha 1)

HRD

23h

Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses. (PubMed, Pathol Res Pract)

Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.

23 hours ago

Journal

ALK (Anaplastic lymphoma kinase) • HRD (Homologous Recombination Deficiency) • NRG1 (Neuregulin 1) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • NTRK (Neurotrophic receptor tyrosine kinase)

HRD • NRG1 fusion • RAD51B mutation • MET fusion

Breast cancer brain metastases genomic profiling identifies alterations targetable by immune-checkpoint and PARP inhibitors. (PubMed, NPJ Precis Oncol)

High PD-L1 protein expression was observed in ER-negative/HER2-negative BCBMs (48.3% vs 50.0% in local BCs, 21.4% in N-CNS). Our data highlights that a high proportion of BCBMs are potentially amenable to treatment with targeted therapeutic agents including PARP inhibitors and ICIs.

1 day ago

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

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)

PD-L1 expression • BRCA2 mutation • HER-2 negative • HRD • ER negative

BRCA2 germline mutation carrier with five malignancies: a case report. (PubMed, Hered Cancer Clin Pract)

Our case study revealed that the pathogenic BRCA2 c.5946del germline variant can be associated with an unusual tumour spectrum, which may lead to a delayed diagnosis of a hereditary tumour predisposition. Thus, upfront genetic testing using large multigene panels or whole-genome sequencing in encouraged, especially in cases with a prominent family history.

2 days ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ATR (Ataxia telangiectasia and Rad3-related protein) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)

BRCA2 mutation • HRD • BRIP1 mutation

BGB-290-103: Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)

P1, N=139, Completed, BeiGene | Phase classification: P1b --> P1

3 days ago

Phase classification • Metastases

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

HRD • BRCA mutation

temozolomide • Partruvix (pamiparib)

Prognostic signature detects homologous recombination deficient in glioblastoma. (PubMed, Transl Cancer Res)

Finally, through univariate and multivariate Cox regression analyses, it was demonstrated that the prognostic model was superior to other prognostic markers. In conclusion, our research has not only demonstrated that a high HRD score is a valid prognostic biomarker in GBM patients but also built a stable prognosis model [odds ratio (OR) 0.18, 95% confidence interval (CI): 0.11-0.23, P<0.001] that is more accurate than conventional prognostic markers such as O6-methylguanine-DNA methyltransferase (MGMT) methylation (OR 0.55, 95% CI: 0.33-0.91, P=0.02).

4 days ago

Journal

HRD (Homologous Recombination Deficiency) • MGMT (6-O-methylguanine-DNA methyltransferase)

HRD • High HRD score

Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib. (PubMed, Genome Med)

These analyses provide valuable insight into patterns of genomic instability and potential drivers of HRD, besides BRCAm, in ovarian cancer and will help guide future research into the potential clinical effectiveness of anti-cancer treatments in ovarian cancer, including PARP inhibitors as well as other precision oncology agents.

4 days ago

Journal • BRCA Biomarker • PARP Biomarker

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • CCNE1 (Cyclin E1) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

PIK3CA mutation • HRD • CCNE1 amplification • PIK3CA amplification • BRIP1 mutation • RAD51C mutation • RAD51D mutation

Lynparza (olaparib)

Homologous recombination deficiency in ovarian cancer: Global expert consensus on testing and a comparison of companion diagnostics. (PubMed, Eur J Cancer)

This manuscript provides detailed information on currently available HRD CDx and up-to-date guidance from global experts on HRD testing in patients with primary and recurrent OC.

4 days ago

Journal • Companion diagnostic • PARP Companion diagnostic

HRD (Homologous Recombination Deficiency)

HRD

KANDOVA: A Study to Evaluate the Safety of KAND567, in Combination with Carboplatin Therapy, in Women with Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov)

5 days ago

Enrollment closed • Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy

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

HRD

carboplatin • KAND567

Roles of CDK12 mutations in PCa development and treatment. (PubMed, Biochim Biophys Acta Rev Cancer)

Due to the poor prognosis of CDK12-mutant PCa patients and the mediocre response to classic standard therapies, HRD and increased neoantigen levels have provided clinicians with new insights into alternative systematic treatments for this novel PCa phenotype. In this review, we summarize the roles of CDK12 mutations in PCa and discuss their clinical value, suggesting that CDK12 potentially represents a target for further research and the development of clinical strategies for PCa.

5 days ago

Review • Journal

AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12)

HRD • CDK12 mutation • MYC expression

Enhancing the detection of clinically relevant biomarkers in advanced uterine and tubo-ovarian carcinomas through genome-wide analysis. (PubMed, Pathol Res Pract)

Comprehensive genomic profiling of advanced-stage TOC and UC via WGS reveals key biomarkers and therapeutic targets, enhancing diagnostic accuracy and advancing personalized medicine in gynecological cancers.

8 days ago

Journal • Tumor mutational burden • BRCA Biomarker • PARP Biomarker • Metastases

TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12)

TMB-H • HRD • BRCA wild-type • CCNE1 amplification

Nicaraven enhances the cytotoxicity of X-ray irradiation in cancer cells with homologous recombination deficiency. (PubMed, Biochem Biophys Res Commun)

These data suggest that the combination of nicaraven with X-ray irradiation selectively increases the cytotoxic effects of X-ray irradiation on HR-deficient cancer cells. Thus, nicaraven might be a valuable agent for cancer therapy, particularly in combination with radiotherapy.

9 days ago

Journal

BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A)

HRD

11d

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

11 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)

11d

Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer (clinicaltrials.gov)

P1, N=42, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

11 days ago

Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset) • CASP3 (Caspase 3)

HRD

Lynparza (olaparib) • Verzenio (abemaciclib)

12d

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

12 days ago

Trial completion

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

HRD • BRCA mutation

Zejula (niraparib)

14d

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.

14 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

14d

Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer. (PubMed, Gynecol Oncol)

Our results demonstrate that in newly diagnosed advanced non-BRCA1/2 ovarian cancer, GIS as a continuous variable is associated with longer PFS and OS. In patients with HRP ovarian cancer, PARPi treatment may be associated with shorter PFS, which warrants further evaluation.

14 days ago

Journal

HRD (Homologous Recombination Deficiency)

HRD

17d

Extensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer. (PubMed, Int J Cancer)

Supervised machine learning of HRD with nucleotide-specific methylation as the input enabled clinically relevant tumor stratification. Taken together, this study provides novel biological and translational insights into HRD in TNBCs.

17 days ago

Journal

HRD (Homologous Recombination Deficiency)

HRD

19d

Whole genome profiling of primary and metastatic adrenocortical carcinoma unravels significant molecular events. (PubMed, Pathol Res Pract)

Comparative analysis between conventional and oncocytic ACC subtypes revealed no significant differences in mutation load, microsatellite instability, or specific gene enrichment. This comprehensive WGS analysis broadens the spectrum of genomic alterations in ACC, highlighting potential molecular targets and differences across subtypes that may inform future therapeutic strategies.

19 days ago

Journal • Tumor mutational burden • Metastases

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • JAK1 (Janus Kinase 1) • RAD51 (RAD51 Homolog A) • ZNF501 (Zinc Finger Protein 501)

TP53 mutation • HRD • HRD signature

21d

COMRADE: Testing the Safety of Different Doses of Olaparib Given Radium-223 for Men With Advanced Prostate Cancer With Bone Metastasis (clinicaltrials.gov)

P1/2, N=133, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2024 --> Apr 2025 | Trial primary completion date: Nov 2024 --> Apr 2025

21 days ago

Trial completion date • Trial primary completion date • Tumor mutational burden

HRD (Homologous Recombination Deficiency) • CD4 (CD4 Molecule)

HRD

OncoPanel™ Assay

Lynparza (olaparib) • Xofigo (radium Ra-223 dichloride)

23d

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.

23 days ago

Journal • BRCA Biomarker • PARP Biomarker

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

HRD • BRCA mutation

24d

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.

24 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

25d

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.

25 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)

26d

Beyond HRD status: Unraveling Genetic Variants Impacting PARP Inhibitor Sensitivity in Advanced Ovarian Cancer. (PubMed, Cancer Res Commun)

P2; Additionally, analysis of BRCA1 variants revealed that truncating variants in exon 11 correlated with clinical benefit when niraparib was combined with bevacizumab. Conclusively, our findings highlight the complexity of PARPi response in AOC and underscore the importance of exploring somatic variants beyond HRD status. Further investigation into exon 11 variants of BRCA1 and the potential of combination treatment is warranted.

26 days ago

Journal • PARP Biomarker • BRCA Biomarker • Metastases

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

HRD

Myriad myChoice® CDx • TruSight Oncology 500 Assay

Avastin (bevacizumab) • Zejula (niraparib)

28d

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.

28 days ago

Journal • BRCA Biomarker • Metastases

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

HRD • BRCA mutation

28d

Homologous recombination deficiency in pancreatic neuroendocrine tumors. (PubMed, Future Oncol)

However, thanks to the SNP analysis, a consistent number of partial or complete single-copy deletions or duplications in several chromosomes. The AmoyDX HRD focus assay performed well on pancreatic samples, despite being originally designed for ovarian cancer and used on samples stored for over a year. Larger studies are needed to further assess the role of HRD assays in pNETs research.

28 days ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

HRD • CHEK2 mutation

AmoyDx® HRD Focus Panel

30d

EANO guideline on molecular testing of meningiomas for targeted therapy selection. (PubMed, Neuro Oncol)

In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence level criteria, no molecular target reached ESCAT I ("ready for clinical use") classification and only mTOR pathway activation and NF2 alterations reached ESCAT II ("investigational") classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.

30 days ago

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

PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KLF4 (Kruppel-like factor 4)

HRD

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.

1 month 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)

Discovery of Pyrazolo[1,5,4-de]quinoxalin-2(3H)-one Derivatives as Highly Potent and Selective PARP1 Inhibitors. (PubMed, J Med Chem)

30 achieved tumor regression in the BRCA1-mutated MDA-MB-436 xenograft model and showed synergistic efficacy in combination with carboplatin in the SUM149PT xenograft model. In the rat hematological toxicity study, 30 exhibited minimal impact on hematological parameters at 25 mg/kg, while AZD5305 at 1 mg/kg caused 56.5% reduction of reticulocyte. Taken together, we discovered compound 30 with a therapeutic index superior to that of PARP1 inhibitors AZD5305 and AZD9574 in the preclinical setting.

1 month ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

BRCA1 mutation • HRD • HRD + BRCA1 mutation

carboplatin • saruparib (AZD5305) • AZD9574

Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database. (PubMed, J Gastroenterol)

Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.

1 month ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

HRD • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • BARD1 mutation

FoundationOne® CDx • OncoGuide™ NCC Oncopanel System

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium

Decoding the pathological and genomic profile of epithelial ovarian cancer. (PubMed, Sci Rep)

We observed that OC clinical and pathological characteristics of these patients from Tunisia were similar to those of Caucasian patients. We identified frequent CNA in this population that need to be confirmed in other sets from Africa.

1 month ago

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

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • H2AX (H2A.X Variant Histone)

PD-L1 expression • PD-L1 overexpression • HER-2 amplification • HER-2 expression • HRD • PD-L1 amplification • HER-2 amplification + PD-L1 expression

Subito: Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer (clinicaltrials.gov)

P3, N=174, Active, not recruiting, The Netherlands Cancer Institute | Trial primary completion date: Oct 2024 --> Jul 2025

1 month ago

Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • HRD (Homologous Recombination Deficiency)

HER-2 negative • HRD

Lynparza (olaparib) • carboplatin • doxorubicin hydrochloride • cyclophosphamide

PARP inhibitors in gliomas: Mechanisms of action, current trends and future perspectives. (PubMed, Cancer Treat Rev)

They have been evaluated both alone and in combination with radiotherapy, temozolomide, anti-angiogenic agents, immunotherapy and other new drugs in newly diagnosed or recurrent glioma...In conclusion, early phase studies have shown promising anti-tumour activity of PARPi that should be confirmed in larger prospective and randomised trials. In addition, the development of novel PARPi with improved blood brain barrier (BBB) penetration and PARP inhibitor activity with new synergistic treatment combinations seems promising and needs to be further explored.

1 month ago

Review • Journal • PARP Biomarker • IO biomarker

HRD (Homologous Recombination Deficiency)

HRD

temozolomide

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

Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)

HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.

1 month ago

Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)

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

Myriad myChoice® CDx

Long-term outcomes of PARP inhibitors in ovarian cancer: survival, adverse events, and post-progression insights. (PubMed, ESMO Open)

We emphasize the importance of long-term follow-up and real-world data coming from international registries to define the efficacy and safety of stopping PARPi at relapse at a pre-specified time. To this point, biomarkers able to identify the patients who will experience long-term remission with PARPi maintenance or develop early resistance are urgently needed to guide treatment decision and duration.

1 month ago

Journal • Adverse events • BRCA Biomarker • PARP Biomarker

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

HRD

Time-Trend Analysis and Risk Factors for Niraparib-Induced Nausea and Vomiting in Ovarian Cancer: A Prospective Study. (PubMed, Cancer Res Treat)

Pre-emptive treatment with antiemetics are required to manage early-phase NINV during niraparib maintenance therapy in patients with risk factors. Additional larger studies are needed to confirm these findings and to develop optimal preventive strategies for NINV.

1 month ago

Journal • BRCA Biomarker • PARP Biomarker

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

HRD • BRCA mutation

Zejula (niraparib)

Molecular Alterations in Paired Epithelial Ovarian Tumors in Patients Treated with Neoadjuvant Chemotherapy. (PubMed, Cancers (Basel))

This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment.

1 month ago

Journal • Tumor mutational burden • BRCA Biomarker

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

BRCA2 mutation • BRCA1 mutation • HRD

Leveraging homologous recombination deficiency for sarcoma : Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma. (PubMed, Pathologie (Heidelb))

We provide a personalized oncological approach to potentially improve the treatment of sarcoma patients. We encourage the evaluation of gene expression signatures to enhance the identification of patients who might benefit from DDR-based therapies.

1 month ago

Journal • PARP Biomarker

HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A)

HRD

HRD Testing Using Illumina TSO500 and Comparison of Two Analysis Pipelines (AMP 2024)

Our preliminary results indicate excellent concordance using Illumina 500+HRD kit with DRAGEN pipeline with previous test results. The concordance appears slightly lower using NxClinical, however, not statistically significant in this small sample set. Of particular interest, our findings suggest that, to reduce the testing costs, the standard TSO500 panel without the additional HRD probe pool, followed by analysis with NxClinical software, may serve as a suitable initial screen.

1 month ago

HRD (Homologous Recombination Deficiency)

HRD

TruSight Oncology 500 Assay

Automation of the New Illumina TruSight Oncology 500 v2 Assay on the Beckman Coulter Biomek i7 Workstation (AMP 2024)

The new TSO500 v2 assay with automated library prep on the Biomek i7 workstation was demonstrated to perform comparably to manual library prep and offers a high-throughput solution to enable comprehensive genomic profiling with a faster, more flexible workflow and easier-to-use reagent kit.

1 month ago

Tumor mutational burden

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)

HRD

TruSight Oncology 500 Assay

HRD Classification by ASCN Diversity and Indel Repair Signatures with Anchored Multiplex PCR and Next-Generation Sequencing (AMP 2024)

Our AMP chemistry-based targeted panel and analysis method enable highly concordant HRD classifications with fewer reads than WGS and other NGS methods, and without requiring paired tumor-normal data or a panel of normals. The HRD module can be combined with any other VariantPlex panel content for simultaneous measurement of HRD, other genomic signatures, and variant calling.

1 month ago

Next-generation sequencing

HRD (Homologous Recombination Deficiency)

HRD

Archer™ VARIANTPlex™ HRD Module