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Open research questions in PARP inhibition in cancer therapy

89 unresolved questions extracted from the limitations and future-work sections of 205 PARP inhibition in cancer therapy papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Limited direct active-active evidence, requiring indirect comparisons among active regimens. Heterogeneity across trials, requiring the use of random-effects models. Sparse safety data for combination regimens, limiting the comparative safety analysis.

    PARP inhibitor-based first-line maintenance therapy for newly diagnosed advanced ovarian cancer across molecular subgroups: an updated systematic review and network meta-analysis · 2026 · DOI

  • Limited trial numbers. Ecological study-level covariates. Heterogeneity within categories. Sparse direct active-active evidence. Limited safety data for combination regimens.

    PARP inhibitor-based first-line maintenance therapy for newly diagnosed advanced ovarian cancer across molecular subgroups: an updated systematic review and network meta-analysis · 2026 · DOI

  • Detecting and managing novel treatment-related adverse events. Removing historical siloing of disciplines to meet patients' needs across disease settings. Coordinating research into the mechanisms of toxicities to mitigate risks and aid in the development of more targeted treatments.

    Oncology must confront hidden side effects · 2026 · DOI

  • Coordinated research into the mechanisms of toxicities can help mitigate risks and aid in the development of more targeted treatments, - Inclusion of populations at risk in the adaptation of current toxicity and quality-of-life reporting

    Oncology must confront hidden side effects · 2026 · DOI

  • Although mammalian PARPs have been extensively characterized, comparatively little is known about PARPs in pathogenic filamentous fungi.

    Biochemical and Mechanistic Characterization of the DNA-dependent Poly(ADP-ribose) Polymerase, MoPARP1, in Magnaporthe oryzae · 2026 · DOI

  • Selinexor, an FDA-approved XPO1 inhibitor, has demonstrated anti-tumor activity in other cancers, but its potential in TGCTs remains unknown.

    XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors · 2026 · DOI

  • Evidence suggests that one such PTM, adenosine 5'-diphosphate (ADP)-ribosylation, is important for viral replication, but the host and viral components involved are poorly understood.

    Zinc-finger PARP proteins ADP-ribosylate alphaviral proteins and are required for interferon-γ–mediated antiviral immunity · 2025 · DOI

  • However, it remains uncertain whether this strategy can or will be translated to the clinic.

    A Critical Appraisal of the Utility of Targeting Therapy-Induced Senescence for Cancer Treatment · 2025 · DOI

  • Therefore, the majority of macrodomain-containing proteins have not been tested towards these additional substrates and were considered to be inactive.

    Family-wide analysis of human macrodomains reveals novel activities and identifies PARG as most efficient ADPr-RNA hydrolase · 2025 · DOI

  • However, overall survival (OS) benefits remain uncertain, and toxic effect profiles emphasize the need for optimized patient and agent selection.

    PARP Inhibitor Maintenance After First-Line Chemotherapy in Advanced-Stage Epithelial Ovarian Cancer · 2025 · DOI

  • This achievement has spurred further research into identifying additional therapeutic targets within the DDR pathway.

    Advancing cancer therapy: new frontiers in targeting DNA damage response · 2024 · DOI

  • While recent findings reported that the automodification of PARP1 promotes its release from the DNA lesions, the potential impact of other ADP-ribosylated proteins on this process remains unknown.

    Histone ADP-ribosylation promotes resistance to PARP inhibitors by facilitating PARP1 release from DNA lesions · 2024 · DOI

  • Background: Limited data are available regarding the anticancer activity of PARP inhibitors (PARPis) in pancreatic cancer with mutations in HRR genes other than BRCA and PALB2.

    PARP Inhibitors in Pancreatic Cancer with Homologous Recombination Repair Gene Mutations: A Single-Institution Experience · 2024 · DOI

  • However, the best therapeutic strategy for recurrence during PARP-i maintenance therapy remains unknown.

    Effects of PARP Inhibitors on Subsequent Platinum-Based Chemotherapy in Patients with Recurrent Ovarian Cancer · 2024 · DOI

  • However, repurposing of PARP inhibitors to treat Acanthamoeba is poorly understood.

    Novel anti-Acanthamoeba effects elicited by a repurposed poly (ADP-ribose) polymerase inhibitor AZ9482 · 2024 · DOI

  • Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive.

    Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling · 2024 · DOI

  • However, the functions and regulatory mechanisms of PARP1 in NB progression still remain to be determined.

    YY1 drives PARP1 expression essential for PARylation of NONO in mRNA maturation during neuroblastoma progression · 2024 · DOI

  • Further investigation of the anti-cancer activity of substituted 2-aminothiophenes - The development of new PARP-1 inhibitors using in silico design and docking studies

    IN-SILICO DRUG DESIGN AND SYNTHESIS OF NOVEL 2- AMINOTHIOPHENE AS ANTI-CANCER AGENTS · 2026 · DOI

  • The need for new therapies that target the different mechanisms of cancer cells - The limited number of PARP-1 inhibitors available for cancer treatment

    IN-SILICO DRUG DESIGN AND SYNTHESIS OF NOVEL 2- AMINOTHIOPHENE AS ANTI-CANCER AGENTS · 2026 · DOI

  • Further investigation of the role of DTX2 in ADPr-Ub production at sites of DNA damage. The development of new tools to study ADPr-Ub and its recognition by proteins.

    Specificity and recognition of the ADP-ribosyl-ubiquitin modification in the DNA damage response · 2026 · DOI

  • The lack of understanding of the specificity and recognition of ADPr-Ub. The need to develop tools to study ADPr-Ub and determine its phenotypic consequences in cellular systems.

    Specificity and recognition of the ADP-ribosyl-ubiquitin modification in the DNA damage response · 2026 · DOI

  • The high rate of disease recurrence in ovarian carcinoma. The development of platinum-resistant disease. The need to identify effective maintenance therapies.

    Comparison of survival outcomes of Olaparib or Olaparib combine with Bevacizumab in patients with primary high-grade serous ovarian carcinoma · 2026 · DOI

  • The study is retrospective in nature. The sample size may be limited. The study only included patients with primary high-grade serous ovarian carcinoma.

    Comparison of survival outcomes of Olaparib or Olaparib combine with Bevacizumab in patients with primary high-grade serous ovarian carcinoma · 2026 · DOI

  • There is a need for more effective and personalized treatment strategies in breast cancer. Current treatment approaches often involve a one-size-fits-all approach. There is a lack of understanding of the mechanisms of chemotherapy resistance.

    Breast cancer chemotherapy in transition: predictive markers, resistance mechanisms, and new treatment approaches · 2026 · DOI

  • The advancement of chemotherapy in breast cancer is moving toward personalization rather than abandonment. Chemotherapy will likely remain essential for many patients, but its delivery is becoming more selective, adaptive, and biologically integrated. Future progress will depend on refining predictive markers, especially through multimodal approaches that combine genomic alterations, immune contexture, molecular subtyping, and dynamic biomarkers such as ctDNA. Better identification of true chemosensitive disease could minimize toxicity in low-benefit populations while enabling rational escalation in high-risk groups. At the same time, overcoming resistance will require moving beyond single-marker thinking. Resistance is rarely explained by one pathway alone; instead, it reflects evolving tumor ecosystems. Integrative profiling before, during, and after treatment may allow clinicians to identify emerging resistant clones and modify therapy accordingly. The neoadjuvant setting remains ideal for this research because it offers serial tissue access and direct assessment of response. Finally, future therapeutic strategies will likely blend chemotargeted agents, and posttherapy with immunotherapy, neoadjuvant residual disease–directed interventions.

    Breast cancer chemotherapy in transition: predictive markers, resistance mechanisms, and new treatment approaches · 2026 · DOI

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89 open questions have been extracted from the limitations and future-work passages of 205 PARP inhibition in cancer therapy papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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