ArticleTranslational lung cancer research2021
In small cell lung cancer patients treated with RRx-001, a downregulator of CD47, decreased expression of PD-L1 on circulating tumor cells significantly correlates with clinical benefit.
Article in Translational lung cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02489903 (A Phase II Study of RRx-001 in Platinum Refractory/Resistant Small Cell Carcinoma, EGFR TKI Resistant EGFR+ T790M Negative Non-Small Cell Lung Cancer, High Grade Neuroendocrine Tumors and Resistant/Refractory Ovarian Cancer Prior to Re-administration of Platinum Based Doublet Regimens), which is not on this map. Cited by 14 papers.
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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.
A Phase II Study of RRx-001 in Platinum Refractory/Resistant Small Cell Carcinoma, EGFR TKI Resistant EGFR+ T790M Negative Non-Small Cell Lung Cancer, High Grade Neuroendocrine Tumors and Resistant/Refractory Ovarian Cancer Prior to Re-administration of Platinum Based Doublet Regimens (QUADRUPLE THREAT)
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Expression of Immune Checkpoint-Associated Proteins for CD24, Siglec-10, CD47, and SIRPα in Breast Phyllodes Tumor.International journal of molecular sciences · 2026Article
- Small cell lung cancer: from immunobiological mechanisms to clinical advances.Frontiers in immunology · 2026Review
- Circulating tumor cells: advancing personalized therapy in small cell lung cancer patients.Molecular oncology · 2025Review
- CD47-mediated tumor microenvironment remodeling: a central mechanism in immune evasion.Acta biochimica et biophysica Sinica · 2025Review
- Targeting the NLRP3 inflammasome for inflammatory disease therapy.Trends in pharmacological sciences · 2025Review
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer.Nature reviews. Clinical oncology · 2024Review
- Landscape and Treatment Options of Shapeshifting Small Cell Lung Cancer.Journal of clinical medicine · 2024Review
- Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation.Cells · 2024Review
- Circulating tumor cells in gastric cancer: developments and clinical applications.Clinical and experimental medicine · 2023Review
- A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation.Drugs · 2023Review
- Repurposing of Commercially Existing Molecular Target Therapies to Boost the Clinical Efficacy of Immune Checkpoint Blockade.Cancers · 2022Review
- Targeting the CD47-SIRPα Innate Immune Checkpoint to Potentiate Antibody Therapy in Cancer by Neutrophils.Cancers · 2022Review
- Targeting CD47/SIRPα as a therapeutic strategy, where we are and where we are headed.Biomarker research · 2022Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundSmall cell lung cancer (SCLC) is the most aggressive lung tumor, characterized by a rapid doubling time and the development of widespread metastases, for which immune checkpoint inhibitors have been approved to overcome T cell anergy. In light of its dismal prognosis, and lack of curative options, new therapies for extensive-disease SCLC are desperately needed.
methodsRRx-001 is a small molecule Myc inhibitor and down-regulates CD47 expression on tumor cells. We evaluated the programmed death-ligand 1 (PD-L1) status of circulating tumor cells (CTCs) pre and post RRx-001 treatment in a phase 2 clinical trial, called QUADRUPLE THREAT, where patients with previously treated SCLC received RRx-001 in combination with a platinum doublet. The trial was registered with ClinicalTrials.gov, number NCT02489903. Fourteen patients with SCLC were analyzed to investigate the association between clinical outcome and PD-L1 expression on CTCs pre and post RRx-001. The correlation between the binary clinical outcome (clinical benefit vs. progressive disease) and the change of PD-L1 expression on CTCs after RRx-001 was analyzed using a logistic regression adjusting for baseline PD-L1 expression.
resultsThe logistic model McFadden goodness of fit score was 0.477. The logistic model analyzing the association between decreased PD-L1 expression on CTCs after RRx-001 and response to reintroduced platinum doublet had an approximate 92.8% accuracy in its prediction of clinical benefit. The estimated receiver operating characteristic (ROC) displayed a ROC area under the curve (AUC) of 0.93 (95% confidence interval, 0.78-0.99).
conclusionsThese results suggest that PD-L1 expression on CTCs decreased after RRx-001 was significantly correlated with response to reintroduced platinum-based doublet therapy. Monitoring PD-L1 expression on CTCs during RRx-001 treatment may serve as a biomarker to predict response to RRx-001-based cancer therapy.
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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.