^
    2d
    PARP inhibitors in testicular germ cell tumors: what we know and what we are looking for. (PubMed, Front Genet)
    However, few responses to PARPis in TGCTs have been detected in patients with BRCA1/2, ATM or CHEK2 mutations, reinforcing the idea that patients should be optimally selected for tailored treatments in the era of personalized medicine. Future preclinical and clinical research is needed to further investigate the molecular mechanisms of cisplatin resistance and to identify novel therapeutic strategies in resistant/refractory TGCTs patients.
    Review • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2)
    |
    CHEK2 mutation
    |
    cisplatin
    2d
    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)
    2d
    All-trans retinoic acid sensitizes epithelial ovarian cancer to PARP inhibition after exposure to cisplatin. (PubMed, Mol Cancer Ther)
    Moreover, a CDDP treatment followed by niraparib maintenance therapy in combination with ATRA improved the survival of EOC-bearing mice. Mechanistically, ATRA down-regulates the expression of these genes and level of intracellular NAD+. Our results suggest that ATRA in conjunction with PARPi represents a promising maintenance therapeutic strategy for EOC.
    Journal • PARP Biomarker
    |
    CHEK1 (Checkpoint kinase 1) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • NAMPT (Nicotinamide Phosphoribosyltransferase)
    |
    cisplatin • Zejula (niraparib)
    2d
    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)
    3d
    Fluzoparib With or Without Bevacizumab for Neoadjuvant Therapy in Advanced Ovarian Cancer (clinicaltrials.gov)
    P2, N=105, Recruiting, Qilu Hospital of Shandong University
    New P2 trial • Combination therapy • Metastases
    |
    Avastin (bevacizumab) • carboplatin • paclitaxel • AiRuiYi (fluzoparib)
    4d
    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.
    Retrospective data • Review • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA (Breast cancer early onset)
    |
    BRCA mutation
    |
    Lynparza (olaparib)
    5d
    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
    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)
    5d
    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)
    6d
    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.
    P3 data • Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA (Breast cancer early onset)
    |
    BRCA mutation
    |
    Lynparza (olaparib) • gemcitabine • paclitaxel • pegylated liposomal doxorubicin • topotecan
    6d
    Next-Generation Sequencing-Guided Treatment of BRCA2-Mutant Metastatic Uterine Leiomyosarcoma With Poly(ADP-ribose) Polymerase Inhibitor Therapy. (PubMed, JCO Precis Oncol)
    No abstract available
    Journal • Next-generation sequencing • BRCA Biomarker • Metastases
    |
    BRCA2 (Breast cancer 2, early onset)
    |
    BRCA2 mutation
    6d
    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
    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)
    6d
    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
    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)
    7d
    Predicting High-Risk Patients with Lung Adenocarcinoma: The Power of Plasma Cell-Related Genes. (PubMed, Oncology)
    Subsequently, we conducted drug sensitivity analysis and immune checkpoint analysis, revealing that the majority of drugs are more sensitive to low-risk patients, while ABT-888, AS601245, and CCT007093 may have greater potential clinical benefits for high-risk patients. Immune checkpoint analysis showed significant differences in the expression of ADORA2A, BTLA, CD276, CD27, CD28, CD40LG, CD48, and TNFRSF14 between high-risk and low-risk patient groups, suggesting their potential as therapeutic targets for LUAD..
    Journal • PARP Biomarker • IO biomarker
    |
    CD276 (CD276 Molecule) • LY9 (Lymphocyte Antigen 9) • CD28 (CD28 Molecule) • CD27 (CD27 Molecule) • TNFRSF14 (TNF Receptor Superfamily Member 14) • BTLA (B And T Lymphocyte Associated) • ADORA2A (Adenosine A2a Receptor) • CD40LG (CD40 ligand) • CD48 (CD48 Molecule) • CASP10 (Caspase 10) • EPSTI1 (Epithelial Stromal Interaction 1)
    |
    veliparib (ABT-888)
    7d
    Activation of cGAS confers PARP inhibitor resistance in ovarian cancer via the TBK1-IRF3 axis. (PubMed, Int J Clin Exp Pathol)
    Our study highlights the crucial function of cGAS signaling in mediating PARPi resistance in ovarian cancer cells. These findings provide valuable novel therapeutic strategies targeting cGAS to improve the efficacy of PARPi-based treatments for ovarian cancer.
    Journal • PARP Biomarker
    |
    IL6 (Interleukin 6) • CGAS (Cyclic GMP-AMP Synthase)
    |
    Lynparza (olaparib)
    7d
    Ion channel modulator DPI-201-106 significantly enhances antitumor activity of DNA damage response inhibitors in glioblastoma. (PubMed, Neurooncol Adv)
    Combination treatment of DPI-201-106 with the CHK1 inhibitor prexasertib or the PARP inhibitor niraparib demonstrated synergistic effects in multiple patient-derived glioblastoma cells both in vitro and in intracranial xenograft mouse models, extending survival of glioblastoma-bearing mice. DPI-201-106 enhances the efficacy of DDR inhibitors to reduce glioblastoma growth. As these drugs have already been clinically tested in humans, repurposing DPI-201-106 in novel combinatorial approaches will allow for rapid translation into the clinic.
    Journal • PARP Biomarker
    |
    ANXA5 (Annexin A5)
    |
    Zejula (niraparib) • prexasertib (ACR-368)
    7d
    Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION) (clinicaltrials.gov)
    P2, N=401, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2024 --> Sep 2025
    Trial completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR mutation • ALK fusion
    |
    Lynparza (olaparib) • cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • pemetrexed
    7d
    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
    Trial completion
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HRD • BRCA mutation
    |
    Zejula (niraparib)
    7d
    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
    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)
    8d
    Application and research progress of synthetic lethality in the development of anticancer therapeutic drugs. (PubMed, Front Oncol)
    With the tremendous success of the PARP inhibitor olaparib in clinical practice, synthetic lethality has become an important field for the discovery and development of anticancer drugs...Currently, many drug candidates that were designed and developed on the basis of the concept of synthetic lethality have entered clinical trials. Taking representative synthetic lethal targets Poly ADP-ribose polymerase 1 (PARP1), Werner syndrome helicase (WRN) and protein arginine methyltransferase 5 (PRMT5) as examples, this article briefly discusses the application and research progress of synthetic lethality in the development of anticancer drugs.
    Review • Journal • Synthetic lethality
    |
    WRN (WRN RecQ Like Helicase)
    |
    Lynparza (olaparib)
    8d
    POLESTAR: Chemotherapy and Pembrolizumab, Followed by Pembrolizumab and Olaparib as Firstline Therapy in Her-2 Negative Gastric/GEJ Adenocarcinoma (clinicaltrials.gov)
    P2, N=31, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Phase classification: P2a --> P2
    Phase classification
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    HER-2 negative
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • capecitabine • oxaliplatin
    8d
    ATLAS-101: A Trial of AMXI-5001 for Treatment in Patients With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=122, Recruiting, AtlasMedx, Incorporated | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Oct 2026 | Trial primary completion date: Jan 2025 --> Aug 2026
    Enrollment open • Trial completion date • Trial primary completion date • Metastases
    |
    AMXI-5001
    9d
    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)
    9d
    Replication stress marker phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer. (PubMed, bioRxiv)
    Our study underscores the importance of considering replication stress markers alongside HR status in therapeutic planning. Our work suggest that this assay could be used throughout a patient's treatment course to expand the number of patients receiving effective therapy while reducing unnecessary toxicity.
    Journal • PARP Biomarker
    |
    RPA2 (Replication Protein A2)
    9d
    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
    Enrollment closed • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • PGR positive • BRCA mutation
    |
    Lynparza (olaparib)
    11d
    Efficacy of olaparib combined with dabrafenib and trametinib for a patient with BRAF mutated and ATM deleted metastatic melanoma. (PubMed, J Eur Acad Dermatol Venereol)
    No abstract available
    Journal • PARP Biomarker • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • ATM mutation • ATM deletion
    |
    Lynparza (olaparib) • Mekinist (trametinib) • Tafinlar (dabrafenib)
    12d
    A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma. (PubMed, Front Oncol)
    The most common adverse events seen were anemia, fatigue, and thrombocytopenia. In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.
    P2 data • Journal • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • 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) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
    |
    FANCA deletion
    |
    Zejula (niraparib)
    12d
    Recent and Future Developments in the Use of Poly (ADP-ribose) Polymerase Inhibitors for Prostate Cancer. (PubMed, Eur Urol Oncol)
    PARPi are active against PCa with HRR mutations, especially in those with germline or somatic BRCA1/2 mutations.  There is still a need to further optimize patient stratification strategies, particularly for combination approaches. Future research should focus on refining predictive biomarkers, improving treatment delivery strategies, and exploring the potential benefits of PARPi in earlier stages of the disease.
    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)
    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.
    Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker
    |
    BRCA (Breast cancer early onset) • DRD (DNA Repair Deficiency)
    |
    DDR • BRCA mutation
    12d
    Olaparib (LYNPARZA) Plus Durvalumab (IMFINZI) in EGFR-Mutated Adenocarcinomas That Transform to Small Cell Lung Cancer (SCLC) and Other Neuroendocrine Tumors (clinicaltrials.gov)
    P2, N=4, Completed, National Cancer Institute (NCI) | Recruiting --> Completed | N=25 --> 4 | Trial completion date: Dec 2026 --> Feb 2024
    Trial completion • Enrollment change • Trial completion date
    |
    BRCA (Breast cancer early onset)
    |
    EGFR mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab)
    12d
    Phase 1 Study of M9466 Combined With Carboplatin and Platinum-based Anticancer Therapy (DDRiver 521) (clinicaltrials.gov)
    P1, N=54, Not yet recruiting, EMD Serono Research & Development Institute, Inc.
    New P1 trial • Combination therapy
    |
    Tecentriq (atezolizumab) • carboplatin • etoposide IV • M9466
    13d
    DTX3L-mediated TIRR nuclear export and degradation regulates DNA repair pathway choice and PARP inhibitor sensitivity. (PubMed, Nat Commun)
    Our work reveals a dual action of DTX3L on TIRR degradation and nuclear exportation and identifies DTX3L as an upstream regulator of the TIRR-53BP1 axis that governs DNA repair pathway choice and PARP inhibitor sensitivity. These findings suggest that TIRR ubiquitination and DTX3L overexpression could be viable biomarkers predicting PARP inhibitor sensitivity in cancers.
    Journal • PARP Biomarker • IO biomarker
    |
    TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    PARP1 overexpression
    13d
    REVOCAN: Safety and Efficacy of AsiDNATM, a DNA Repair Inhibitor, Administered Intravenously in Addition to PARP Inhibitors in Patients With Relapsed Platinum Sensitive Ovarian Cancer Already Treated With PARP Inhibitors Since at Least 6 Months (clinicaltrials.gov)
    P1/2, N=13, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=26 --> 13 | Trial completion date: Oct 2023 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Apr 2024; Treatment availability issue: The manufacturer of AsiDNA™ decided to cease production to develop an improved version, and the contract ensuring access to this molecule has expired.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    Lynparza (olaparib) • Zejula (niraparib) • Rubraca (rucaparib) • AsiDNA (etidaligide)
    13d
    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)
    13d
    AMPLITUDE: A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) (clinicaltrials.gov)
    P3, N=696, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: May 2027 --> Nov 2027
    Trial completion date • Combination therapy • Metastases
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    Zejula (niraparib) • abiraterone acetate • prednisone
    14d
    A Study of Rucaparib and Nivolumab in People With Leiomyosarcoma (clinicaltrials.gov)
    P2, N=20, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
    Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • Rubraca (rucaparib)
    14d
    UTOLA: UTerin OLAparib (clinicaltrials.gov)
    P2, N=147, Completed, ARCAGY/ GINECO GROUP | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    BRCA (Breast cancer early onset)
    |
    Lynparza (olaparib)
    14d
    TOMAS2: Randomized Trial in Advanced, Metastatic or Unresectable Soft Tissue Sarcoma After Failure of Standard Treatments. (clinicaltrials.gov)
    P2, N=130, Completed, Italian Sarcoma Group | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    Lynparza (olaparib) • Yondelis (trabectedin)
    14d
    Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer (clinicaltrials.gov)
    P1/2, N=50, Recruiting, Xing Xie | Trial primary completion date: Jan 2024 --> Dec 2024
    Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    BRCA2 mutation • BRCA1 mutation • MUC16 elevation
    |
    AiRuiYi (fluzoparib) • arsenic trioxide
    15d
    Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response Pathway-Deficient Neoplasms. (PubMed, JCO Precis Oncol)
    Niraparib failed to meet the prespecified efficacy end point for response. However, clinical benefit was suggested in a proportion of patients who had a confirmed mBAP1, supporting further investigation.
    P2 data • Journal • BRCA Biomarker • PARP Biomarker
    |
    PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    PTEN mutation • ARID1A mutation • BAP1 mutation
    |
    Zejula (niraparib)
    15d
    Enhancing PARP inhibitor efficacy using reduction-responsive nanoparticles encapsulating NADP. (PubMed, J Mater Chem B)
    The combined effects of elevated NADP+ levels and olaparib synergistically suppress tumor cell growth. Overall, our study offers a promising strategy for the clinical application of NADP+.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    BRCA2 mutation • BRCA1 mutation
    |
    Lynparza (olaparib)
    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.
    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)
    16d
    Parpvax: Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy (clinicaltrials.gov)
    P1/2, N=104, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Oct 2024
    Trial completion • Trial completion date • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Zejula (niraparib)