PARP inhibitor
Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of targeted anticancer agents that exploit defects in DNA damage repair pathways, particularly homologous recombination (HR).
Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of targeted anticancer agents that exploit defects in DNA damage repair pathways, particularly homologous recombination (HR). PARP enzymes play a central role in detecting and repairing single-strand DNA breaks; when inhibited, unresolved breaks collapse replication forks into double-strand breaks. In tumor cells already harboring deficiencies in HR — such as those with loss-of-function mutations in BRCA1 or BRCA2 DNA repair associated genes — this dual impairment of repair pathways leads to synthetic lethality, resulting in selective cancer cell death while largely sparing normal cells. olaparib, one of the earliest and most clinically validated agents in this class, exemplifies the mechanism and has been approved across multiple HR-deficient tumor types including ovarian, breast, and prostate cancers.
The therapeutic utility of PARP inhibitors is closely tied to the concept of BRCAness — a broader genomic phenotype characterized by deficient homologous recombination repair (HRD), even in the absence of germline BRCA mutations. The presence of PTEN loss and other HR pathway alterations has been associated with sensitivity to this drug class. Understanding and expanding the HRD-positive patient population, overcoming intrinsic and acquired resistance, and identifying synergistic combination strategies represent the principal frontiers of contemporary PARP inhibitor research.
Where the papers sit
14 papers from the last 6 months study PARP inhibitor directly · updated from PubMed 5 Oct 2026
Study type 1 clinical trial · 2 observational · 2 human data · 8 preclinical · 1 unclassified
Themes 3 themes · 1 paradigm shift
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PARP Therapy Across Cancers
Clinical benefit and resistance to PARP inhibition are being assessed across ovarian, breast and prostate cancers. In ovarian cancer, POSTN+ myofibroblasts, the STING-WNT axis and acidic microenvironments link immunosuppression to resistance, while p300 inhibition offers a reversal strategy. Platinum-sensitive ovarian cancer is being tested for PARP rechallenge, and TSL-1502 extends trials to germline BRCA-mutated, HER2-negative breast cancer. Prostate studies remain mainly observational or combination-focused, with overall survival and safety as key endpoints.
6 papers · 42.9%
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DNA Repair Vulnerabilities
Homologous recombination profiling is moving treatment toward DNA-repair-defined subgroups rather than uniform PARP sensitivity. HRR hyperactivation is presented as a vulnerability in neuroendocrine cervical cancer, while profiling exposes actionable defects and four genomic-instability subtypes in cervical and hereditary breast cancers. Prostate cancer strategies are expanding beyond androgen-receptor inhibition through repair-directed options. Mitochondrial NADP(H)-dependent de novo dTMP synthesis emerges as a mechanism that counteracts PARP inhibitor cytotoxicity.
5 papers · 35.7%
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DNA Damage Targeting in Cancer
DNA-damage targeting is being extended to BRCA-proficient or treatment-resistant solid tumours. DA1 is designed to make BRCA-proficient triple-negative breast cancer vulnerable to PARP inhibition by suppressing PI3K/AKT/mTOR signaling. HER3-DXd combined with PARP inhibition increases antitumor activity in non-small-cell lung cancer, while a structure-guided SYK inhibitor represents a separate targeted approach in triple-negative disease. The shared direction is pathway-based therapy, but the studies do not establish one common biomarker or clinical standard.
3 papers · 21.4%
PARP inhibitor response is governed by metabolic and microenvironmental resistance circuits, not homologous-recombination status alone
Mitochondrial NADP(H)-dependent dTMP biosynthesis in PARP-inhibitor-nonresponsive tumor cells 42784515Sep and p300-mediated acidic-microenvironment resistance in epithelial ovarian cancer 42467549Jul separately show that the HR-deficiency-centered account is incomplete. The first study found that PARP-inhibitor nonresponse was maintained through mitochondrial NADP(H) metabolism and mito-dTMP production regardless of HR status, while the second showed that extracellular acidosis enhanced DNA-damage repair and reduced PARP1 trapping through a p300-dependent pathway. Thus, PARP-inhibitor sensitivity cannot be inferred from HR status alone: mitochondrial metabolism or tumor acidity can independently impose resistance, and cotargeting STAT3 or p300 provides a way to restore antitumor activity.
Papers
The 14 papers from the last 6 months that study PARP inhibitor directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
PARP Therapy Across Cancers (6)
- Patterns of Poly(ADP-Ribose) Polymerase Inhibitor Use and Overall Survival in United States Veterans With Prostate Cancer. Clinical genitourinary cancer · 27 Aug 2026 PMID 42660761
- Randomized phase 2 trial of a PARP inhibitor TSL-1502 in germline BRCA-mutated, HER2-negative locally advanced/metastatic breast cancer. Signal transduction and targeted therapy · 9 Aug 2026 PMID 42572030
- Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: a multicenter retrospective study. International journal of clinical oncology · 7 Aug 2026 PMID 42566090
- Targeting p300 Reverses Acidic Microenvironment-Induced PARP Inhibitor Resistance. Cancer research · 17 Jul 2026 PMID 42467549
- Genomic instability drives POSTN+ myofibroblasts via STING-WNT axis to promote immunosuppression and PARPi resistance in ovarian cancer. Science translational medicine · 27 May 2026 PMID 42202048
- Clinical Benefit and Safety of Combined Immunotherapy and Targeted Therapy in Prostate Cancer. International journal of cancer · 22 Apr 2026 PMID 42017392
DNA Repair Vulnerabilities (5)
- Multi-omics profiling reveals homologous recombination repair hyperactivation as a therapeutic vulnerability in neuroendocrine cervical carcinoma. Signal transduction and targeted therapy · 4 Oct 2026 PMID 42830288
- Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors. Proceedings of the National Academy of Sciences of the United States of America · 24 Sept 2026 PMID 42784515
- Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model. Scientific reports · 29 Jul 2026 PMID 42527451
- Novel therapeutic strategies for metastatic castration‑resistant prostate cancer: Beyond androgen receptor pathway inhibition (Review). International journal of oncology · 17 Apr 2026 PMID 41992975
- Delineation of the heterogeneity underlying genomic instability in hereditary breast cancers reveals four disease subtypes. Experimental & molecular medicine · 16 Apr 2026 PMID 41991965
DNA Damage Targeting in Cancer (3)
- PARP inhibition enhances the antitumor activity of HER3-DXd in non-small cell lung cancer. Cell reports. Medicine · 21 Aug 2026 PMID 42628527
- Discovery of DA1 as PARP inhibitor for the treatment of BRCA-proficient triple negative breast cancer by suppressing the PI3K/AKT/mTOR signaling pathway. Bioorganic & medicinal chemistry · 30 Jul 2026 PMID 42531674
- Integrating Machine Learning and Structure-Guided Discovery of a Novel Type II SYK Inhibitor for Treating Triple-Negative Breast Cancer. Journal of medicinal chemistry · 17 Jun 2026 PMID 42304805
By study type
Clinical trials (1)
- Randomized phase 2 trial of a PARP inhibitor TSL-1502 in germline BRCA-mutated, HER2-negative locally advanced/metastatic breast cancer. Signal transduction and targeted therapy · 9 Aug 2026 PMID 42572030
Observational studies and case reports (2)
- Patterns of Poly(ADP-Ribose) Polymerase Inhibitor Use and Overall Survival in United States Veterans With Prostate Cancer. Clinical genitourinary cancer · 27 Aug 2026 PMID 42660761
- Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: a multicenter retrospective study. International journal of clinical oncology · 7 Aug 2026 PMID 42566090
Human data, design not indexed (2)
- Novel therapeutic strategies for metastatic castration‑resistant prostate cancer: Beyond androgen receptor pathway inhibition (Review). International journal of oncology · 17 Apr 2026 PMID 41992975
- Delineation of the heterogeneity underlying genomic instability in hereditary breast cancers reveals four disease subtypes. Experimental & molecular medicine · 16 Apr 2026 PMID 41991965
Preclinical: animal, cell and lab studies (8)
- Multi-omics profiling reveals homologous recombination repair hyperactivation as a therapeutic vulnerability in neuroendocrine cervical carcinoma. Signal transduction and targeted therapy · 4 Oct 2026 PMID 42830288
- Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors. Proceedings of the National Academy of Sciences of the United States of America · 24 Sept 2026 PMID 42784515
- PARP inhibition enhances the antitumor activity of HER3-DXd in non-small cell lung cancer. Cell reports. Medicine · 21 Aug 2026 PMID 42628527
- Discovery of DA1 as PARP inhibitor for the treatment of BRCA-proficient triple negative breast cancer by suppressing the PI3K/AKT/mTOR signaling pathway. Bioorganic & medicinal chemistry · 30 Jul 2026 PMID 42531674
- Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model. Scientific reports · 29 Jul 2026 PMID 42527451
- Targeting p300 Reverses Acidic Microenvironment-Induced PARP Inhibitor Resistance. Cancer research · 17 Jul 2026 PMID 42467549
- Integrating Machine Learning and Structure-Guided Discovery of a Novel Type II SYK Inhibitor for Treating Triple-Negative Breast Cancer. Journal of medicinal chemistry · 17 Jun 2026 PMID 42304805
- Genomic instability drives POSTN+ myofibroblasts via STING-WNT axis to promote immunosuppression and PARPi resistance in ovarian cancer. Science translational medicine · 27 May 2026 PMID 42202048
Unclassified: not yet indexed with MeSH (1)
- Clinical Benefit and Safety of Combined Immunotherapy and Targeted Therapy in Prostate Cancer. International journal of cancer · 22 Apr 2026 PMID 42017392
Written from 14 PubMed abstracts, each one listed by PMID above. Published: 2026-07-08. Last written: 2026-09-26 by GPT. Drafted by language models from published abstracts; not medical advice.