ArticleInvestigational new drugs2013
The PARP inhibitor ABT-888 synergizes irinotecan treatment of colon cancer cell lines.
Article in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 67 citations in OpenAlex.
- A phase 2 randomised study of veliparib plus FOLFIRI±bevacizumab versus placebo plus FOLFIRI±bevacizumab in metastatic colorectal cancer.British journal of cancer · 2019Trial
- Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy.Scientific reports · 2025Article
- OBI-992, a Novel TROP2-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models.Molecular cancer therapeutics · 2025Article
- Article
- A carrier-free supramolecular nano-twin-drug for overcoming irinotecan-resistance and enhancing efficacy against colorectal cancer.Journal of nanobiotechnology · 2023Article
- NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors.Cancer research communications · 2023Article
- Combined PARP and Dual Topoisomerase Inhibition Potentiates Genome Instability and Cell Death in Ovarian Cancer.International journal of molecular sciences · 2022Article
- Article
- Targeting the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Colorectal Cancer.Cancers · 2022Review
- Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Therapeutic Potential of PARP Inhibitors in the Treatment of Gastrointestinal Cancers.Biomedicines · 2021Review
- Poly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment.World journal of gastrointestinal oncology · 2021Review
- Vulnerability to low-dose combination of irinotecan and niraparib in ATM-mutated colorectal cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer.Frontiers in pharmacology · 2021Review
- Review
- BReast CAncer (BRCA) gene mutations as an emerging biomarker for the treatment of gastrointestinal malignancies.Chinese clinical oncology · 2020Review
- Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib.Investigational new drugs · 2019Article
- Exploiting DNA repair defects in colorectal cancer.Molecular oncology · 2019Review
- PARP1 rs1805407 Increases Sensitivity to PARP1 Inhibitors in Cancer Cells Suggesting an Improved Therapeutic Strategy.Scientific reports · 2019Article
- A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours.British journal of cancer · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Poly [ADP-ribose] polymerase-1 (PARP-1) localizes rapidly to sites of DNA damage and has been associated with various repair mechanisms including base excision repair (BER) and homologous recombination/non-homologous end joining (HRR/NHEJ). PARP-1 acts by adding poly-ADP ribose side chains to target proteins (PARylation) altering molecular interactions and functions. Recently small molecule inhibitors of PARP-1 have been shown to have significant clinical potential and third generation PARP inhibitors are currently being investigated in clinical trials. These drugs alone or in combination with radio/chemotherapy have resulted in meaningful patient responses and an increase in survival in metastatic breast cancer cases bearing BRCA-deficient or triple negative tumors and BRCA-deficient ovarian cancer patients. ABT-888, a potent PARP-1 inhibitor, sensitizes many cancer cells in-vitro and in-vivo to temozolomide. As such, we hypothesized that colon cancers would be sensitized to the DNA damaging chemotherapeutic agents, oxaliplatin and irinotecan, by ABT-888. Using colon cancer cell lines significant synergy was observed between ABT-888 and irinotecan at concentrations of ABT-888 as low as 0.125 μM. The level of synergy observed correlated with the degree of PARP1 inhibition as measured biochemically in cell lysates. ABT-888 at concentrations of 0.5-4 μM resulted in synergy with oxaliplatin. Furthermore, 24 h post treatment combinations of ABT-888/irinotecan generally resulted in increased G2/M cell cycle arrest and increased levels of DNA damage, followed by increased levels of apoptosis 48 h post treatment. In conclusion this study suggests that ABT-888 may be a clinically effective adjuvant to current colon cancer therapies that include the use of irinotecan and/or oxaliplatin.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.