ArticleBreast cancer research and treatment2018
Combination of anthracyclines and anti-CD47 therapy inhibit invasive breast cancer growth while preventing cardiac toxicity by regulation of autophagy.
Article in Breast cancer research and treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 55 citations in OpenAlex.
- A Phase 1/2 study of ontorpacept (TTI-621) in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma.British journal of cancer · 2026Trial
- Low-dose DOX-polygodial nanosystem modulates the CD47/CALR axis for safer triple negative breast cancer treatment.Nanoscale advances · 2026Article
- Targeting CD47-mediated cancer senescence, a novel strategy for cancer immunotherapy.Frontiers in immunology · 2026Review
- Human Single-Nucleus RNA Sequencing Identifies CD47 as a Therapeutic Target for Doxorubicin-Induced Cardiomyopathy.Circulation · 2025Article
- Dietary influences on chemotherapy sensitivity and cardiotoxicity modulated by IRE1 targeting in triple-negative breast cancer in female mice.Physiological reports · 2025Article
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Tolerating CD47.Clinical and translational medicine · 2024Review
- Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives.Frontiers in oncology · 2024Review
- A novel CD47-blocking peptide fused to pro-apoptotic KLA repeat inhibits lung cancer growth in mice.Cancer immunology, immunotherapy : CII · 2023Article
- Review
- New immunotherapy strategies for patients with sarcomas: highlights from the 2023 ASCO annual meeting.Journal of hematology & oncology · 2023Article
- Targeting CD47-SIRPa axis shows potent preclinical anti-tumor activity as monotherapy and synergizes with PARP inhibition.NPJ precision oncology · 2023Article
- CD47-Dependent Regulation of Immune Checkpoint Gene Expression and MYCN mRNA Splicing in Murine CD8 and Jurkat T Cells.International journal of molecular sciences · 2023Article
- M2b macrophages protect against doxorubicin induced cardiotoxicity via alternating autophagy in cardiomyocytes.PloS one · 2023Article
- Targeting the CD47-SIRPα Axis: Present Therapies and the Future for Cutaneous T-cell Lymphoma.Cells · 2022Review
- Review
- CD47 interactions with exportin-1 limit the targeting of mJournal of cell communication and signaling · 2022Article
- CD47-SIRPα blocking-based immunotherapy: Current and prospective therapeutic strategies.Clinical and translational medicine · 2022Review
- CD47 antibody protects mice from doxorubicin-induced myocardial damage by suppressing cardiomyocyte apoptosis.Experimental and therapeutic medicine · 2022Article
- Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications.Journal of Zhejiang University. Science. B · 2022Review
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundA perennial challenge in systemic cytotoxic cancer therapy is to eradicate primary tumors and metastatic disease while sparing normal tissue from off-target effects of chemotherapy. Anthracyclines such as doxorubicin are effective chemotherapeutic agents for which dosing is limited by development of cardiotoxicity. Our published evidence shows that targeting CD47 enhances radiation-induced growth delay of tumors while remarkably protecting soft tissues. The protection of cell viability observed with CD47 is mediated autonomously by activation of protective autophagy. However, whether CD47 protects cancer cells from cytotoxic chemotherapy is unknown.
methodsWe tested the effect of CD47 blockade on cancer cell survival using a 2-dimensional high-throughput cell proliferation assay in 4T1 breast cancer cell lines. To evaluate blockade of CD47 in combination with chemotherapy in vivo, we employed the 4T1 breast cancer model and examined tumor and cardiac tissue viability as well as autophagic flux.
resultsOur high-throughput screen revealed that blockade of CD47 does not interfere with the cytotoxic activity of anthracyclines against 4T1 breast cancer cells. Targeting CD47 enhanced the effect of doxorubicin chemotherapy in vivo by reducing tumor growth and metastatic spread by activation of an anti-tumor innate immune response. Moreover, systemic suppression of CD47 protected cardiac tissue viability and function in mice treated with doxorubicin.
conclusionsOur experiments indicate that the protective effects observed with CD47 blockade are mediated through upregulation of autophagic flux. However, the absence of CD47 in did not elicit a protective effect in cancer cells, but it enhanced macrophage-mediated cancer cell cytolysis. Therefore, the differential responses observed with CD47 blockade are due to autonomous activation of protective autophagy in normal tissue and enhancement immune cytotoxicity against cancer cells.
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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.