^
    15d
    Cooperative molecular interaction networks govern PARP1 inhibitor selectivity and binding affinity. (PubMed, PLoS Comput Biol)
    To explore the molecular determinants of ligand selectivity, we focus on four clinically relevant PARP inhibitors-two PARP1-selective (saruparib and NMS-P118) and two non-selective (veliparib and olaparib) inhibitors-and perform atomistic potential-of-mean-force calculations of the PARP1 catalytic binding domain in the presence of these molecules. Progressively increasing the number of mutations markedly reduces binding stability, with distinct residue combinations exerting two primary effects: destabilization of the final bound state and the emergence of energetic barriers along the ligand association pathway. Together, our results provide a coherent mechanistic framework for understanding PARP1 selectivity and informs the rational design of next-generation inhibitors with improved efficacy and safety.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA (Breast cancer early onset) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
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    BRCA mutation
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    Lynparza (olaparib) • veliparib (ABT-888) • saruparib (AZD5305) • NMS-P118
    21d
    S1513: FOLFIRI or Modified FOLFIRI and Veliparib as Second Line Therapy in Treating Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P2, N=123, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed
    Trial completion
    |
    CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    irinotecan • veliparib (ABT-888) • leucovorin calcium • fluorouracil topical
    22d
    Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P2, N=83, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027
    Trial completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA (Breast cancer early onset)
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    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRCA mutation
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    cisplatin • gemcitabine • veliparib (ABT-888)
    29d
    Advances in PARP Inhibition in Improving Outcomes of Breast Cancer, Ovarian Cancer, and Other Solid Tumors: Journey of Discovery, Development, and Clinical Updates of Talazoparib. (PubMed, Drug Des Devel Ther)
    Among PARPi, Talazoparib (Talzenna®) is a potent therapy for patients with locally advanced or metastatic BC (mBC) with germline BRCA mutations (gBRCAm) and HER2-negative status, demonstrating the highest potency (IC50 = 0.57 nM), which is 4-10 times lower than that of other PARP inhibitors; olaparib (2.0 nM), rucaparib (1.9 nM), and veliparib (4.7 nM), indicating superior efficacy. The latest advancements in talazoparib research, including all related clinical trials (Phase 1-3) for the treatment of BC, OC, and other solid tumors (STs), are also summarized. A comprehensive analysis of all clinical trials involving talazoparib, whether as monotherapy or in combination with other drugs, elucidates its potential to improve clinical outcomes, address drug resistance, and explore synergistic combinations with other PARPi or novel agents, thereby providing insights into the clinical utility of talazoparib.
    Review • 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) • BRCA (Breast cancer early onset)
    |
    HER-2 negative • BRCA mutation
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • Rubraca (rucaparib) • veliparib (ABT-888)
    1m
    Veliparib and Topotecan Hydrochloride in Treating Patients With Solid Tumors, Relapsed or Refractory Ovarian Cancer, or Primary Peritoneal Cancer (clinicaltrials.gov)
    P1/2, N=88, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2026 --> Mar 2027
    Trial completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    veliparib (ABT-888) • topotecan
    1m
    Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=97, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027
    Trial completion date
    |
    CELLSEARCH®
    |
    temozolomide • veliparib (ABT-888)
    2ms
    Neoadjuvant treatment regimens associated with pathological complete response in triple-negative breast cancer: a systematic review and network meta-analysis. (PubMed, Expert Rev Anticancer Ther)
    Twenty-five treatment nodes were formed, with paclitaxel (P) or docetaxel (D) + anthracycline - based (A) chemotherapy as the main comparator. Compared with PA-based + cyclophosphamide, higher pCR rates were observed with PA-based + carboplatin + pembrolizumab + cyclophosphamide (OR 3,04) and PA - based + carboplatin + veliparib + cyclophosphamide (OR 2,67). When DA-based + cyclophosphamide was the comparator, DA-based + cyclophosphamide + bevacizumab (OR 1,67) increased pCR. The SUCRA ranked PA-based + carboplatin + pembrolizumab, paclitaxel + carboplatin + atezolizumab, and DA-based + lobaplatin as most effective. Platinum agents, PARP inhibitors, and immune checkpoint inhibitors were associated with higher pCR rates in early-stage TNBC. CRD42025640277.
    Retrospective data • Review • Journal
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    HER-2 (Human epidermal growth factor receptor 2)
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    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • paclitaxel • docetaxel • cyclophosphamide • veliparib (ABT-888) • lobaplatin (D19466)
    2ms
    Cyclophosphamide and Veliparib in Treating Patients With Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027
    Trial completion date
    |
    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)
    |
    BRCA1 mutation • HER-2 negative • PGR positive • BRCA mutation
    |
    cyclophosphamide • veliparib (ABT-888)
    3ms
    A071102: Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (clinicaltrials.gov)
    P2/3, N=447, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026
    Trial completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    temozolomide • veliparib (ABT-888)
    3ms
    Veliparib, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery and Liver or Kidney Dysfunction (clinicaltrials.gov)
    P1, N=94, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027
    Trial completion date
    |
    carboplatin • paclitaxel • veliparib (ABT-888)
    3ms
    Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia (clinicaltrials.gov)
    P2, N=25, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026
    Trial completion date
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    RAD51 (RAD51 Homolog A)
    |
    carboplatin • veliparib (ABT-888) • topotecan
    3ms
    Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov)
    P1/2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026
    Trial completion date
    |
    ERCC1 (Excision repair cross-complementation group 1) • XRCC1 (X-Ray Repair Cross Complementing 1)
    |
    carboplatin • paclitaxel • veliparib (ABT-888)