ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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109 citing papers in PubMed, 179 citations in OpenAlex.
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- Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients With Relapsed-Sensitive or Refractory Small-Cell Lung Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.Nature communications · 2026Article
- Efficacy and safety of poly ADP-ribose polymerase inhibitors (PARPis) in extensive-stage small-cell lung cancer (ES-SCLC) treatment: a systematic review and meta-analysis.Journal of thoracic disease · 2025Article
- Alterations and correlation between DNA damage and repair response and PD-L1 expression in non-small cell lung cancers.BMC cancer · 2025Article
- DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer.iScience · 2025Article
- Exploring lung cancer microenvironment: pathways and nanoparticle-based therapies.Discover oncology · 2025Review
- Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies.Recent patents on anti-cancer drug discovery · 2025Review
- Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.Molecular cancer · 2024Article
- Review
- A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.Nature communications · 2024Article
- A novel dopamine receptor D2 antagonist (ONC206) potentiates the effects of olaparib in endometrial cancer.Cancer biology & therapy · 2023Article
- Obesity promotes breast epithelium DNA damage in women carrying a germline mutation inScience translational medicine · 2023Article
- Stellettin B Sensitizes Glioblastoma to DNA-Damaging Treatments by Suppressing PI3K-Mediated Homologous Recombination Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Current Evidence and Future Perspectives about the Role of PARP Inhibitors in the Treatment of Thoracic Cancers.OncoTargets and therapy · 2023Review
- Targeting the DNA Damage Response Machinery for Lung Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy.Nature reviews. Clinical oncology · 2022Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeSmall cell lung carcinoma (SCLC) is an aggressive malignancy affecting nearly 30,000 people annually in the United States. We have previously identified elevated PARP1 levels in SCLC and demonstrated in vitro sensitivity to the PARP inhibitors AZD 2281 and AG014699. Here, we evaluate activity of a novel, potent PARP inhibitor, BMN 673, and identify markers of response as a basis for developing predictive markers for clinical application. EXPERIMENTAL
designInhibition of SCLC proliferation by BMN 673 was assayed in vitro and effects on tumor growth were measured in SCLC xenograft models. Protein expression and pathway activation was assessed by reverse phase protein array and western blot analysis. PARP inhibition was confirmed using a PAR ELISA.
resultsWe demonstrate striking, single agent activity of BMN 673 in SCLC cell lines and xenografts, with single agent BMN 673 exhibiting in vivo activity similar to cisplatin. Sensitivity to BMN 673 was associated with elevated baseline expression levels of several DNA repair proteins, whereas greater drug resistance was observed in SCLC models with baseline activation of the PI3K/mTOR pathway. Furthermore, we developed and confirmed these data with a novel "DNA repair score" consisting of a group of 17 DNA repair proteins.
conclusionsElevated expression of multiple DNA repair proteins, as well as a corresponding "DNA repair protein score," predict response to BMN 673 in in vitro SCLC models. These observations complement recent work in which PI3K inhibition sensitizes breast cancer models to PARP inhibition, suggesting cooperation between DNA repair and PI3K pathways.
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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.