veliparib (ABT-888) / AbbVie - LARVOL DELTA

Role of DNA damage sensing and TP53 function as modulators of sensitivity to calicheamicin-based antibody-drug conjugates (ADCs) for acute leukemia (ASH 2025) - "Better survival of some patients with the CD33 ADC, gemtuzumab ozogamicin (GO), and the CD22 ADC, inotuzumab ozogamicin (InO), validate these efforts, but these ADCs are ineffective in many others...CLM-induced cytotoxicity was assessed in vitro in the presence/absence of a Mouse Double Minute 2 homolog (MDM2) inhibitor (idasanutlin), Ataxia-Telangiectasia Mutated (ATM) inhibitor (AZD1390, lartesertib), Ataxia Telangiectasia and Rad3-related (ATR) inhibitor (ceralasertib), Checkpoint Kinase 1 and Checkpoint Kinase 1 (Chk1/Chk2) inhibitors (prexasertib, BML-277), and poly(ADP-ribose) polymerase (PARP) inhibitor (veliparib)... Our studies identify ATM, MDM2, and TP53 as key modulators of CLM-induced cytotoxicity in acute leukemia cells. These results support further evaluation of combination therapies with corresponding small molecule inhibitors (currently pursued in patients with other cancers) toward possible clinical testing as novel strategies to increase the efficacy..."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Ataxia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Immunology • Leukemia • Movement Disorders • Primary Immunodeficiency • CD22 • CD33 • CDKN1A • FBXW7 • TP53

Haematological toxicities with targeted drugs in tumors: A systematic review and network meta-analysis of randomized controlled trials (ASH 2025) - "1 patient treated with sorafenib plus chemotherapy was reported to have died as a result of pancytopenia and 1 patient treated with chemotherapy (gemcitabine plus cisplatin) died due to anemia. Our study confirmed that chemotherapy with or without a placebo, one targeted drug with chemotherapy was associated with more severe hematologic toxicities compared with the use of one targeted drug, tepotinib plus gefitinib, tivantinib plus erlotinib. In the targeted drug monotherapy category, for the primary outcome, we found that alectinib and gefitinib had a higher risk of all-grade (grade 1-5) and severe-grade (grade 3-5) anemia, respectively...Ganitumab plus chemotherapy had the highest risk of grade 1-5 anemia and thrombocytopenia. Afatinib plus chemotherapy had the highest risk of grade 3-5 anemia and thrombocytopenia. Ramucirumab plus chemotherapy had the highest risk of grade 1-5 and 3-5 neutropenia. Veliparib plus chemotherapy had the highest risk of grade 1-5 and 3-5..."

Retrospective data • Review • Febrile Neutropenia • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia

PARP1 facilitates transcriptional activity and stability of the BCL6 protein and is a therapeutic target in BCL6 expressing lymphomas (ASH 2025) - "While we showed that BCL6 is PARylated, BCL6 PARylation was not necessary for BCL6 TR,since reconstitution of PARP1 Crispr/Cas9-edited cells with wild type PARP1 or E988K PARP1 mutantsuppressed BCL6 reporter activity to levels observed in the non-manipulated 293T cells expressing BCL6.Since PARylation can regulate protein stability we performed cycloheximide (CHX) pulse-chaseexperiments showing progressive decrease in BCL6 protein levels over time, that was enhanced in thepresence of Olaparib and rescued by proteasome inhibitor MG132...Olaparib and Veliparib induced a pronounced decrease in colonyformation and cell viability as assessed by the MTS assay and potentiated similar effects of BCL6 inhibitor79-6. Both PARP1 inhibitors and BCL6 inhibitor 79-6 induced apoptosis and cell death in a cell line specificmanner. These combinations may be considered for clinical evaluation.Overall, for the first time our studies show that PARP1 plays an essential and direct role in..."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • BCL6 • MYC • PARP1

The transition from myelodysplastic neoplasm to secondary acute myeloid leukemia is revealed by molecular analysis, while functional drug screening demonstrates novel sensitivity patterns with clinical implication (ASH 2025) - "There are only a limited number of agentsthat are FDA approved for treatment of MDS including BCL2 and IDH inhibitors, hypomethylating agents(HMAs), ESAs, luspatercept and imetelstat...For MDS patients, weidentified the most effective agents with the proportion of sensitive samples noted in parentheses:mitoxantrone (100%), olutasidenib (78%), venetoclax (67%), dinaciclib (67%), trametinib (67%), olaparib(56%), GSK3368715 (56%), pacritinib (44%), lenalidomide (44%), fludarabine (55%), tasquinimod (44%),veliparib (44%). For sAML patients, we identified lenalidomide, olutasidenib, GSK3368715 have high DSSsin all tested samples, while fludarabine, fedratinib, tasquinimod, trametinib, veliparib, mitoxantrone andolaparib have high DSSs in 75% of the AML samples...Cancer Research 2024), and our samples included SF3B1 and U2AF1 mutations.Summary This study of the transition of MDS to sAML highlights molecular changes and reveals new drugsensitivity with agents that could be..."

Biomarker • Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • FLT3 • JAK2 • NRAS • PTPN11 • SF3B1 • U2AF1

Tumor Imaging Heterogeneity Index-Inspired Insights into the Unveiling Tumor Microenvironment of Breast Cancer. (PubMed, Int J Mol Sci) - "The "immune+/replication+" showed sensitivity to pembrolizumab (OR = 10.192, p < 0.001) and veliparib/carboplatin (OR = 5.184, p = 0.006), while "immune-/replication-" responded poorly to pembrolizumab (OR = 0.086, p < 0.001). Additionally, "immune+/replication-" had the best distant recurrence-free survival (DRFS), whereas "immune-/replication+" had the worst (log-rank p = 6 × 10-4, HR = 5.45). By linking imaging heterogeneity directly to molecular subtypes and therapeutic response, this framework provides a robust, non-invasive surrogate for genomic profiling and a strategic tool for personalized neoadjuvant therapy selection."

Biomarker • Heterogeneity • Journal • Breast Cancer • Oncology • Solid Tumor

Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP-ribose) glycohydrolase inhibitor. (PubMed, FEBS Open Bio) - "Interestingly, HCT116RPDD cells exhibited greater sensitivity to γ-ray irradiation and the nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 than the parental HCT116 cells, yet showed comparable sensitivity to 5-FU, cisplatin, and PARP inhibitors olaparib, talazoparib, and veliparib. Furthermore, we observed that HCT116RPDD cells tended to maintain slightly higher levels of intracellular NAD+/NADH and ATP compared to parental HCT116 cells. These findings suggest that cancer cells employ a mechanism to regulate NAD+ and ATP levels, thereby avoiding cell death from intracellular PAR accumulation through coordinated PARP-PARG regulation."

Journal • Colorectal Cancer • Oncology • Solid Tumor • NAMPT

Lost in translation: Do preclinical studies predict clinical failure in GBM? (SNO 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (SNO 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (WFNOS 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Oncology • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (WFNOS 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Glioma • Oncology • Solid Tumor

Unveiling the power of PARP inhibitors: a meta-analysis on newly diagnosed advanced ovarian cancer maintenance therapy. (PubMed, Expert Rev Anticancer Ther) - "Notably, senaparib showed superior PFS efficacy compared to veliparib and niraparib. PARPi showed efficacy in improving PFS as maintenance therapy for newly diagnosed advanced OC, although no OS advantage was observed. PROSPERO (CRD420251020275)."

Journal • Retrospective data • Review • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

Radiosensitization Effect of PARP Inhibitor Talazoparib Involves Decreasing Mitochondrial Membrane Potential and Induction of Cellular Senescence. (PubMed, Curr Issues Mol Biol) - "ER10 values for talazoparib, olaparib rucaparib, ABT888 and niraparib were 1.5, 1.8, 2.8, 1.4, and 1.4, respectively. When the p21 gene was knocked down, both the decrease in mitochondrial membrane potential and senescence level were attenuated, suggesting that p21 is involved in senescence induction after γ-irradiation combined with talazoparib treatment. Taken together, we showed that PARP inhibitor talazoparib treatment in combination with γ-irradiation causes cellular senescence in lung cancer cells, involving p21 function."

Journal • Lung Cancer • Oncology • Solid Tumor • CDKN1A

Veliparib and Temozolomide in Treating Patients With Acute Leukemia (clinicaltrials.gov) - P1 | N=66 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • T Acute Lymphoblastic Leukemia • RAD51

Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • ER • HER-2 • PGR

Determination of veliparib metabolic stability in the human liver microsomes using a hydrophilic interaction UPLC-MS/MS quantitative method: greenness assessment with an in silico study for ADME, DEREK alarms and metabolic lability. (PubMed, Analyst) - "Chromatographic differentiation of VLP and ceritinib (internal standard) was conducted utilizing a Luna 3 µm HILIC column (200 Å: 50 × 2 mm, Ea), with an isocratic mobile phase at 0.35 mL min-1 comprising 0.1% HCOOH acid in ACN (90%) and 10 mM NH4COOH in water (pH 3.2) at 10%. Enhancing the metabolic stability can enable more convenient dosage regimens, improving the overall therapeutic experience for patients. In silico research indicates that minor structural alterations to the methoxy group or the pyrrolidine moiety (96% metabolically labile) in the drug design may improve the safety profile and the metabolic stability of novel derivatives relative to VLP."

Journal • Oncology

ABT-888 With Modified FOLFOX6 in Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=64 | Completed | Sponsor: Georgetown University | Unknown status ➔ Completed

Trial completion • Breast Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2

ACNS1721: Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations (clinicaltrials.gov) - P2 | N=38 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • BRAF

Veliparib, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=81 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Breast Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • ER • HER-2 • PGR

PARP Inhibitor Maintenance After First-Line Chemotherapy in Advanced-Stage Epithelial Ovarian Cancer: A Systematic Review and Meta-Analysis. (PubMed, JAMA Netw Open) - "Observed treatment efficacy and toxic effects varied across PARP inhibitor regimens; for example, the risk ratio for any recurrence or death in the overall study group ranged from 0.53 (95% CI, 0.40-0.70) for senaparib to 0.83 (95% CI, 0.68-1.00) for olaparib, while the risk ratio for high-grade adverse events ranged from 1.15 (95% CI, 0.64-2.06) for veliparib to 4.73 (95% CI, 2.77-8.07) for niraparib. In this study, no subgroup showed an association between first-line PARP inhibitor maintenance therapy in advanced-stage EOC and improved OS, and findings suggest that the consistency of associated PFS benefits may vary, particularly in homologous recombination proficient and BRCA wild type tumors. Variability in efficacy and toxic effects across subgroups and PARP inhibitor regimens underscores the importance of individualized treatment decisions."

Clinical • Journal • Retrospective data • Review • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

Preclinical evaluation of a 68 Ga/ 177 Lu theranostic targeting PARP for PARP-expressing cancers (EANM 2025) - "Radioactivity uptakes were effectively blocked by the addition of excess, structurally different PARPi: Veliparib, talazoparib, rucaparib and/or olaparib (100 mM) (Fig. Conclusion Taken together, we showed that KK02 selectively accumulates in tumor tissues while rapidly clearing from non-target healthy tissues. These findings highlight the strong potential of 68 Ga- and 177 Lu-labeled KK02 as a theranostic pair, allowing for the identification and personalized treatment of PARP-expressing cancers."

Preclinical • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • PARP1

Influence of differential source patterns in the detection of signals of disproportionate reporting for PARP inhibitors. (PubMed, Front Drug Saf Regul) - "The reporting patterns of four marketed oncology drugs, namely, olaparib, rucaparib, niraparib, and talazoparib, and an investigational drug, veliparib, were compared to those of a diverse set of eight clinically observed SDR, namely, fatigue, asthenia, anaemia, thrombocytopenia, neutropenia, insomnia, intestinal obstruction, and pneumonitis. Therefore, SDR detected from matched drug-event source patterns in ICSR databases should be challenged during signal validation. Class SDR for drugs with differential source patterns (such as fatigue, asthenia, anaemia, thrombocytopenia, and neutropenia for all PARP inhibitors) usually involve correcting opposite drug-event source patterns."

Journal • CNS Disorders • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Inflammation • Insomnia • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Sleep Disorder • Thrombocytopenia

Acute Toxicity in SWOG 1706, a Randomized Trial Comparing Radiotherapy for Inflammatory Breast Cancer with and without Concurrent Olaparib (ASTRO 2025) - "Consistent with American trials of veliparib and rucaparib, and contrasting with a French trial of olaparib that used considerably higher doses of olaparib (up to 200 mg bid) with different RT techniques and had only 8.3% acute radiation dermatitis, this study, limited to inflammatory disease, suggests a clinically relevant increase in toxicity with concurrent administration of breast and nodal RT with bolus and boost even with low dose olaparib (25 mg bid). As PARP inhibitors become more commonly used, caution is appropriate, particularly if considering concurrent administration during breast radiotherapy outside of the investigational context."

Clinical • Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • MUTYH

Multicenter Stroke Preclinical Assessment Network Analysis of Cardiovascular Risk Factor Subgroups Treated With the Poly(ADP-Ribose) Polymerase Inhibitor Veliparib. (PubMed, J Am Heart Assoc) - "Veliparib improved functional outcome in aging mice. Because ischemic stroke predominantly occurs in the aging population, further research into the benefit of PARP inhibitors in aged animal models of stroke is warranted."

Journal • Preclinical • Cardiovascular • Genetic Disorders • Ischemic stroke • Obesity

Targeting PIM-2 and PARP1 Induces MICA Expression on Multiple Myeloma Cells to Activate NK Cells Through NKG2D Binding (IMS 2025) - "Our findings suggest that the concurrent application of PIM-2 and PARP1 inhibitors can significantly induce MICA expression on MM cells, thereby enhancing NK cell activation through NKG2D binding. This novel mechanism may restore NK cell function and represents a promising therapeutic strategy for multiple myeloma patients. Further investigations are warranted to elucidate the detailed mechanisms underpinning how SMI-16a and ABT888 induce DNA damage and subsequently enhance MICA expression in MM cells."

Hematological Malignancies • Multiple Myeloma • GZMB • MICA • NKG2D • PARP1

Effectiveness and Safety of PARP Inhibitors in Ovarian Cancer: An Umbrella Review of Systematic Reviews and Meta-Analyses. (PubMed, Crit Rev Oncol Hematol) - "These findings support the continued use of PARPi as maintenance therapy in biomarker-selected ovarian cancer populations, while promoting the need for individualized risk-benefit assessment and further research into resistance mechanisms and predictive biomarkers."

Journal • Review • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • BRCA