^
    6d
    Co-regulator activity of Mediator of DNA Damage Checkpoint 1 (MDC1) is associated with DNA repair dysfunction and PARP inhibitor sensitivity in lobular carcinoma of the breast. (PubMed, bioRxiv)
    We tested whether this HR dysfunction could indeed be exploited using PARP inhibition and found that talazoparib treatment produced a durable growth suppression in vitro and in multiple ILC xenografts in vivo...ILC are rarely associated with biomarkers of HR deficiency, and as such patients are rarely eligible for treatment with PARP inhibitors. Our work suggests ILC present with a previously unappreciated form of HR dysfunction, linked to ILC-specific genomic activity of ER and MDC1, which imparts sensitivity to PARP inhibition.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    ER (Estrogen receptor) • BRCA (Breast cancer early onset) • DRD (DNA Repair Deficiency)
    |
    ER positive • DDR
    |
    Talzenna (talazoparib)
    7d
    A Study to Learn About the Safety of TALZENNA for the Treatment of Breast Cancer (clinicaltrials.gov)
    P=N/A, N=37, Not yet recruiting, Pfizer
    New trial
    |
    BRCA (Breast cancer early onset)
    |
    Talzenna (talazoparib)
    9d
    A Study to Learn About the Safety of TALZENNA in People With Prostate Cancer. (clinicaltrials.gov)
    P=N/A, N=104, Not yet recruiting, Pfizer
    New trial • Metastases
    |
    BRCA (Breast cancer early onset)
    |
    Talzenna (talazoparib)
    13d
    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
    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)
    15d
    Talazoparib plus enzalutamide versus olaparib plus abiraterone acetate and niraparib plus abiraterone acetate for metastatic castration-resistant prostate cancer: a matching-adjusted indirect comparison. (PubMed, Prostate Cancer Prostatic Dis)
    Results suggest that TALA + ENZA may provide improvements in clinical outcomes relative to OLAP + AAP and NIRA + AAP in 1 L mCRPC; however, inherent limitations associated with the complexity of the analyses must be considered.
    Journal • PARP Biomarker • Metastases
    |
    HRD (Homologous Recombination Deficiency)
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Xtandi (enzalutamide) • abiraterone acetate
    16d
    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.
    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)
    17d
    Indirect targeting of MYC and direct targeting in combination with chemotherapies are more effective than direct mono-targeting in triple negative breast cancer. (PubMed, Transl Oncol)
    We developed paclitaxel-, doxorubicin-, and cisplatin-resistant MDA-MB-231 cells to study MYC's role in upregulating DNA repair genes during drug resistance development...The combined use of asiRNA-VP (Vinylphosphonate) with dacomitinib or talazoparib was synthetic lethal in TNBC cell lines...We confirmed that MYC knockdown upregulated cFLIP, BCL2, STAT1, pSTAT1, STAT2, and cleaved saspase-3 in both TNBC and non-small cell lung cancer (NSCLC) cell lines. Finally, we recommend a combination treatment approach that synergizes with MYC inhibition rather than monotherapy or indirect targeting via upstream regulators such as the BRD4 and RRM2 genes or selective modulation at the protein level to suppress anti-apoptotic genes (cFLIP and BCL2) at the same time.
    Journal • Combination therapy • PARP Biomarker • IO biomarker
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • RAD51 (RAD51 Homolog A) • BRD4 (Bromodomain Containing 4) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • CFLAR (CASP8 and FADD-like apoptosis regulator) • STAT2 (Signal transducer and activator of transcription 2)
    |
    MYC amplification • RRM2 overexpression • PARP1 overexpression
    |
    cisplatin • paclitaxel • doxorubicin hydrochloride • Talzenna (talazoparib) • Vizimpro (dacomitinib)
    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.
    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)
    1m
    Alternative lengthening of telomere-based immortalization renders H3G34R -mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens. (PubMed, Neuro Oncol)
    Our preclinical and clinical data strongly support the further development of PARPis together with DNA damage stress-inducing treatment regimens for DHG-H3G34R_ATRX.
    Journal • PARP Biomarker
    |
    ATRX (ATRX Chromatin Remodeler) • RAD51 (RAD51 Homolog A)
    |
    Talzenna (talazoparib) • Zejula (niraparib) • irinotecan • topotecan
    1m
    Real-World Evidence on Prescribing Patterns and Clinical Outcomes of Metastatic Breast Cancer Patients Treated with PARP Inhibitors: The Mayo Clinic Experience. (PubMed, Clin Breast Cancer)
    In real-world practice, PARPis are well-tolerated with promising TTF in gBRCA1/2 and gPALB2 carriers. Further studies will delineate the clinical efficacy of PARPis in other MBC subsets, such as sBRCA mutations, HER2-positive disease, and CNS metastasis.
    Clinical data • Journal • HEOR • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HER-2 positive
    |
    Lynparza (olaparib) • Talzenna (talazoparib)
    1m
    Circulating Tumor DNA (ctDNA) Testing in TALAPRO-2 Complements Tumor Testing to Gain a Greater Understanding of the Metastatic Castration-Resistant Prostate Cancer (mCRPC) Mutational Landscape (AMP 2024)
    Introduction: TALAPRO-2 (NCT03395197) demonstrated that first-line talazoparib + enzalutamide significantly improved radiographic progression-free survival versus placebo + enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC). These results are supportive of the ability of F1LCDx to sensitively detect alterations in HRR genes, and the likely overall modest impact of CHiP in calling HRR gene alteration status in this study. These results support the complementary benefits of ctDNA testing to tumor tissue testing in assessing current disease alteration status, particularly AR.
    BRCA Biomarker • PARP Biomarker • Circulating tumor DNA • Metastases
    |
    BRCA2 (Breast cancer 2, early onset) • AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDK12 (Cyclin dependent kinase 12) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2)
    |
    BRCA2 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Talzenna (talazoparib) • Xtandi (enzalutamide)
    2ms
    Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929. (PubMed, J Thorac Oncol)
    Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.
    P2 data • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    SLFN11 (Schlafen Family Member 11)
    |
    Tecentriq (atezolizumab) • Talzenna (talazoparib)
    2ms
    Talazoparib in Combination With Belinostat for Metastatic Breast Cancer, Metastatic Castration Resistant Prostate Cancer, and Metastatic Ovarian Cancer (clinicaltrials.gov)
    P1, N=26, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HR positive • HER-2 negative
    |
    Talzenna (talazoparib) • Beleodaq (belinostat)
    2ms
    TRIO-US L-07: Talazoparib and Low-Dose Temozolomide in Treating Participants With Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=28, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025
    Trial completion date • Trial primary completion date
    |
    temozolomide • Talzenna (talazoparib)
    2ms
    Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study. (PubMed, Eur J Cancer)
    Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.
    P3 data • Journal • PARP Biomarker • Metastases
    |
    HRD (Homologous Recombination Deficiency)
    |
    Talzenna (talazoparib) • Xtandi (enzalutamide)
    2ms
    Talazoparib and Gemtuzumab Ozogamicin for the Treatment of CD33 Positive Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=24, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Jun 2024 | Trial primary completion date: Apr 2025 --> May 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    CD33 (CD33 Molecule)
    |
    Talzenna (talazoparib) • Mylotarg (gemtuzumab ozogamicin)
    2ms
    Targeted therapy approaches for epithelial-mesenchymal transition in triple negative breast cancer. (PubMed, Front Oncol)
    These include inhibitors of signaling pathways such as TGF-β, Wnt/β-catenin, Notch, TNF-α/NF-κB and EGFR, as well as immune checkpoint inhibitors, such as pembrolizumab, 2laparib, and talazoparib have been widely explored. This article reviews recent developments in EMT in TNBC invasion and metastasis and potential targeted therapy strategies.
    Review • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • TNFA (Tumor Necrosis Factor-Alpha) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    HER-2 expression • ER expression
    |
    Keytruda (pembrolizumab) • Talzenna (talazoparib)
    2ms
    The evolution of a luminal breast cancer to a triple-negative and its impact on disease control with sacituzumab govitecan. (PubMed, Recenti Prog Med)
    Approximately 15% of TNBC patients have a germline mutation in BRCA1 and/or BRCA2, and for these patients, innovative therapeutic options such as olaparib and talazoparib, which are PARP inhibitors, are available. Sacituzumab govitecan (SG) is a humanized monoclonal antibody-drug conjugate directed against the surface antigen of human trophoblastic cells (Trop-2) expressed in approximately 90% of TNBC, coupled with SN-38, the active metabolite of irinotecan, a topoisomerase I inhibitor. Here, we present the case of a woman who was initially diagnosed with localized luminal B breast cancer (ER-positive; HER2-negative) and was treated with curative therapy. However, she later experienced a recurrence with metastatic TNBC (ER-negative/HER2-negative) and received treatment with sacituzumab govitecan, which resulted in prolonged disease control.
    Journal • 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) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
    |
    PD-L1 expression • ER positive • BRCA1 mutation • HER-2 negative • ER negative • HER-2 negative + ER positive
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • irinotecan • Trodelvy (sacituzumab govitecan-hziy)
    2ms
    PARP Pioneers: Using BRCA1/2 Mutation-targeted Inhibition to Revolutionize Breast Cancer Treatment. (PubMed, Curr Pharm Des)
    Olaparib and talazoparib are PARP inhibitors (PARPi) are being employed for the monotherapies in case of the deleterious germline HER2-negative and BRCA-mutated breast cancer. The PARPi have been found its place in the all different types of Breast Cancers and have shown potential benefits. The purpose of this review is to provide an update on the oral poly(ADP-ribose) polymerase (PARP)inhibitors for the improvement in the treatment and management of Breast Cancer.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • 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 • HER-2 negative • BRCA mutation
    |
    Lynparza (olaparib) • Talzenna (talazoparib)
    2ms
    Erratum: Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib. (PubMed, JCO Precis Oncol)
    No abstract available
    PK/PD data • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    BRCA2 mutation • BRCA1 mutation
    |
    Talzenna (talazoparib)
    2ms
    Exploratory analyses of homologous recombination repair (HRR) gene subgroups and potential associations with secondary efficacy endpoints in the HRR-deficient population of TALAPRO-2 (TP-2) (DGHO 2024)
    Introduction: TP-2 (NCT03395197) demonstrated statistically significant improvement in rPFS with 1L talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with mCRPC with and without HRR gene alterations (HRRm; prospectively determined). Broad differential efficacy benefit was evident for TALA+ENZA vs PBO+ENZA across multiple molecular subgroups and was most pronounced for the BRCA1 - PALB2 - BRCA2 axis and CDK12.
    Clinical • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Talzenna (talazoparib) • Xtandi (enzalutamide)
    3ms
    Targeting lipid metabolism to improve PARP inhibitor response in BRCA-associated TNBC (SITC 2024)
    Methods Transcriptomic analysis of baseline or on-treatment (PARPi, talazoparib) biopsies from patients with BRCA-associated TNBC from the TALAVE clinical trial (NCT03964532) were assessed using the NanoString-IO360™ and Digital Spatial Profiling (DSP) platforms. Tumor-bearing mice (K14-Cre/Brca1f/f/p53f/f ) were treated with vehicle or PARPi (olaparib) for 5 days and gene expression profiling, flow cytometry and mass spectrometry-based metabolome analysis were utilized to determine the metabolic profile of tumors. To inhibit lipid synthesis, mice were treated with fatostatin (SREBP1 inhibitor) or denifanstat (FASN inhibitor)...Ethics Approval The present study was approved by BWH CMM IACUC, protocol number is 2020N000142 and by Dana-Farber Cancer Institute, protocol number is 20–627. Study drugs were provided by Pfizer, as part of an alliance between Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
    BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • BRCA (Breast cancer early onset)
    |
    PD-L1 expression
    |
    nCounter® PanCancer IO 360™ Panel
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • denifanstat (TVB-2640)
    3ms
    Isoxazole compounds: Unveiling the synthetic strategy, in-silico SAR & toxicity studies and future perspective as PARP inhibitor in cancer therapy. (PubMed, Eur J Med Chem)
    PARP inhibitors, such as Olaparib, Rucaparib, Niraparib, and Talazoparib have been approved in a number of cancers including BRCA 1/BRCA2 associated malignancies although there are many difficulties as therapeutical resistance. It emphasizes that isoxazole-based PARP inhibitors compounds could be novel anti-cancer drugs. Through this review, we hope to grow a curiosity in additional explorations of isoxazole-based PARP inhibitors and their applications in the trends of novel insights towards precision cancer therapy.
    Review • Journal
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib)
    3ms
    PET Imaging Using 89Zr Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention (EPR) in Prostate Cancer. (PubMed, Mol Cancer Ther)
    We developed two 89Zr-radiolabeled nanocarriers based on 4-armed-starPEG40kDa with or without talazoparib (TLZ), a potent PARPi, as surrogates for the PEG-TLZ4 therapeutic scaffold. For PET imaging, PEG-DFB4 and PEG-DFB1-TLZ3 were radiolabeled with 89Zr by replacing one or all four TLZ on PEG-TLZ4 with deferoxamine B (DFB)...Although heterogeneous, prostate cancer xenografts had low EPR. These starPEG nanocarriers could be used as PET imaging surrogates to predict drug delivery and efficacy.
    Journal
    |
    CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
    |
    Talzenna (talazoparib)
    3ms
    Enhancing targeted therapy by combining PI3K and AKT inhibitors with or without cisplatin or vincristine in medulloblastoma cell lines in vitro. (PubMed, Biomed Pharmacother)
    This study provides pre-clinical evidence that AKT inhibitors combined with PI3K inhibitors, cisplatin, or vincristine exhibit additive/synergistic anti-MB activity, and lower doses could be used. The latter also applied to one MB line grown as spheroids, further supporting their future potential use.
    Preclinical • Journal
    |
    FGFR (Fibroblast Growth Factor Receptor)
    |
    cisplatin • Ibrance (palbociclib) • Talzenna (talazoparib) • Piqray (alpelisib) • Balversa (erdafitinib) • adavosertib (AZD1775) • Truqap (capivasertib) • vincristine
    3ms
    Talazoparib Plus Enzalutamide in Patients With HRR-Deficient mCRPC: Practical Implementation Steps for Oncology Nurses and Advanced Practice Providers. (PubMed, Clin J Oncol Nurs)
    This review and hypothetical case study illustrate the role of oncology nurses and APPs in the administration of talazoparib plus enzalutamide and the management of adverse events to ensure safe and effective use in clinical practice. Oncology nurses and APPs play an important role in the dosing and administration of talazoparib plus enzalutamide and can recognize and manage adverse events in patients with HRR-deficient mCRPC.
    Review • Journal • Metastases
    |
    HRD (Homologous Recombination Deficiency)
    |
    Talzenna (talazoparib) • Xtandi (enzalutamide)
    3ms
    PERSEVERE: Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer (clinicaltrials.gov)
    P2, N=197, Active, not recruiting, Bryan Schneider, MD | Recruiting --> Active, not recruiting
    Enrollment closed • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
    |
    Keytruda (pembrolizumab) • Talzenna (talazoparib) • capecitabine • Itovebi (inavolisib)
    3ms
    Molecular mechanism of PARP inhibitor resistance. (PubMed, Oncoscience)
    Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.
    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)
    3ms
    Integrating PARP Inhibitors in mCRPC Therapy: Current Strategies and Emerging Trends. (PubMed, Cancer Manag Res)
    Interestingly, antitumor activity was also observed irrespective of DDR gene mutations, highlighting BRCAness phenotype with androgen receptor blockade resulting in synergistic activity between ARSIs and PARPi. In this review, we discuss the clinical efficacy and safety data of the combination of PARPi plus ARSI in all Phase 3 randomized controlled trials (RCTs), emphasizing strategies for patient selection and highlighting emerging trends based on clinical trial data.
    Clinical • Review • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    Talzenna (talazoparib)
    3ms
    Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression. (PubMed, NPJ Precis Oncol)
    This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.
    Journal • PARP Biomarker
    |
    RAD51 (RAD51 Homolog A) • CHD1 (Chromodomain Helicase DNA Binding Protein 1)
    |
    CHD1 deletion • RAD51 mutation
    |
    Lynparza (olaparib) • Talzenna (talazoparib)
    3ms
    TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (clinicaltrials.gov)
    P2, N=3791, Recruiting, American Society of Clinical Oncology | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Jun 2026
    Trial completion date • Trial primary completion date • Tumor mutational burden • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Yervoy (ipilimumab) • Ibrance (palbociclib) • Zelboraf (vemurafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • sunitinib • Perjeta (pertuzumab) • Cotellic (cobimetinib) • Talzenna (talazoparib) • Verzenio (abemaciclib) • Stivarga (regorafenib) • Lytgobi (futibatinib) • Tukysa (tucatinib) • Torisel (temsirolimus) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    3ms
    Talazoparib Monotherapy in PALB2 Mutation Associated Advanced Breast Cancer (clinicaltrials.gov)
    P2, N=30, Recruiting, Stanford University | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative • PALB2 mutation
    |
    Talzenna (talazoparib)
    3ms
    Uncovering naringin's anticancer mechanisms in glioblastoma via molecular docking and network pharmacology approaches. (PubMed, Sci Rep)
    The molecular dynamic approach and MM-PBSA investigation along with PCA study revealed that the complex of Naringin, with 4ZZZ (PARP1) and, 2ABL (ABL1), are highly stable compared to that of imatinib and talazoparib. Cytotoxicity assay was performed on two different glioblastoma cell lines C6 and U87MG cells. Naringin demonstrates a higher cytotoxic potency against U87MG human glioblastoma cells compared to C6 rat glioma cells.
    Journal
    |
    ABL1 (ABL proto-oncogene 1)
    |
    imatinib • Talzenna (talazoparib)
    3ms
    Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations. (PubMed, Int J Mol Sci)
    We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACis), poly(ADP-ribose) polymerase inhibitors (PARPis), and decitabine in breast (MDA-MB-231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cancer cell lines that were exposed to HDACi (panobinostat or vorinostat), PARPi (talazoparib or olaparib), decitabine, or their combinations. These results indicate that HDACi, PARPi, and decitabine combinations should be further explored in these tumor types. Further clinical validation is warranted to assess their safety and efficacy.
    Journal • PARP Biomarker • Epigenetic controller
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CASP3 (Caspase 3) • ANXA5 (Annexin A5)
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • decitabine • Zolinza (vorinostat) • Farydak (panobinostat)
    4ms
    Talazoparib Plus Enzalutamide After Progression to Abiraterone in Metastatic Prostate Cancer: (TEAM PC) (clinicaltrials.gov)
    P2, N=78, Recruiting, Fundacion Oncosur
    New P2 trial • Metastases
    |
    AR expression
    |
    Talzenna (talazoparib) • Xtandi (enzalutamide) • abiraterone acetate
    4ms
    LUNG-MAP Sub-Study: Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial) (clinicaltrials.gov)
    P2; Active, not recruiting --> Completed
    Trial completion • Tumor mutational burden • Metastases
    |
    STK11 (Serine/threonine kinase 11)
    |
    STK11 mutation
    |
    FoundationOne® CDx
    |
    Bavencio (avelumab) • Talzenna (talazoparib)
    4ms
    Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib. (PubMed, JCO Precis Oncol)
    We conclude that [18F]FTT can image target engagement by PARPi, but larger studies are needed to determine whether [18F]FTT uptake can predict response to PARPi and whether uptake of [18F]FTT in bone marrow may be an early predictor of hematologic toxicity.
    PK/PD data • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    Talzenna (talazoparib)
    4ms
    A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1; Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    BRACAnalysis CDx™
    |
    Talzenna (talazoparib)
    4ms
    Talazoparib and Axitinib for People With Previously Treated Advanced Kidney Cancer (clinicaltrials.gov)
    P1/2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
    |
    Talzenna (talazoparib) • Inlyta (axitinib)
    4ms
    PARLuNET: PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours (clinicaltrials.gov)
    P1, N=24, Recruiting, Peter MacCallum Cancer Centre, Australia | Trial completion date: Dec 2025 --> Jun 2029 | Trial primary completion date: Dec 2025 --> Jun 2029
    Trial completion date • Trial primary completion date • Metastases
    |
    Talzenna (talazoparib)
    4ms
    Talazoparib enhances resection at DSBs and renders HR-proficient cancer cells susceptible to Polθ inhibition. (PubMed, Radiother Oncol)
    We propose that talazoparib promotes low-dose, CtIP/MRE11-dependent resection and increases the reliance of irradiated HR-proficient cancer cells, on Polθ-mediated alt-EJ. Combination of Polθ inhibitors with talazoparib suppresses this option and causes further radiosensitization. The results suggest that Polθ inhibition may be exploited to maximize talazoparib radiosensitization of HR-proficient tumors in the clinic.
    Journal • PARP Biomarker
    |
    MRE11A (MRE11 homolog, double strand break repair nuclease)
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • Rubraca (rucaparib) • veliparib (ABT-888) • ART558
    5ms
    TALASUR: TALazoparib and Avelumab as Maintenance Therapy in Platinum-Sensitive Metastatic or Locally Advanced URothelial Carcinoma (clinicaltrials.gov)
    P2, N=50, Recruiting, Centre Francois Baclesse | Trial completion date: Dec 2023 --> Dec 2025
    Trial completion date • Metastases
    |
    Bavencio (avelumab) • Talzenna (talazoparib)