ArticleNeoplasia (New York, N.Y.)2015
Heparanase mediates a novel mechanism in lapatinib-resistant brain metastatic breast cancer.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma.Cancers · 2023Article
- Revisiting the Syndecans: Master Signaling Regulators with Prognostic and Targetable Therapeutic Values in Breast Carcinoma.Cancers · 2023Review
- TME-targeted approaches of brain metastases and its clinical therapeutic evidence.Frontiers in immunology · 2023Review
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management.Biomolecules · 2021Review
- Review
- The Role and Therapeutic Value of Syndecan-1 in Cancer Metastasis and Drug Resistance.Frontiers in cell and developmental biology · 2021Review
- Non-Anticoagulant Heparins as Heparanase Inhibitors.Advances in experimental medicine and biology · 2020Review
- Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity.Molecules (Basel, Switzerland) · 2018Review
- Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Review
- BRCA1 expression serves a role in vincristine resistance in colon cancer cells.Oncology letters · 2017Article
- Heparanase augments insulin receptor signaling in breast carcinoma.Oncotarget · 2017Article
- Heparanase regulation of cancer, autophagy and inflammation: new mechanisms and targets for therapy.The FEBS journal · 2017Review
- Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Overexpression of suppressor of IKBKE 1 is associated with vincristine resistance in colon cancer cells.Biomedical reports · 2016Article
- Mechanisms of heparanase inhibitors in cancer therapy.Experimental hematology · 2016Review
- Heparanase: From basic research to therapeutic applications in cancer and inflammation.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2016Review
- Chemotherapy induces expression and release of heparanase leading to changes associated with an aggressive tumor phenotype.Matrix biology : journal of the International Society for Matrix Biology · 2016Article
- Article
- Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.Cancers · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Heparanase (HPSE) is the dominant mammalian endoglycosidase and important tumorigenic, angiogenic, and pro-metastatic molecule. Highest levels of HPSE activity have been consistently detected in cells possessing highest propensities to colonize the brain, emphasizing the therapeutic potential for targeting HPSE in brain metastatic breast cancer (BMBC). Lapatinib (Tykerb) is a small-molecule and dual inhibitor of human epidermal growth factor receptor1 and 2 (EGFR and HER2, respectively) which are both high-risk predictors of BMBC. It was approved by the US Food and Drug Administration for treatment of patients with advanced or metastatic breast cancer. However, its role is limited in BMBC whose response rates to lapatinib are significantly lower than those for extracranial metastasis. Because HPSE can affect EGFR phosphorylation, we examined Roneparstat, a non-anticoagulant heparin with potent anti-HPSE activity, to inhibit EGFR signaling pathways and BMBC onset using lapatinib-resistant clones generated from HER2-transfected, EGFR-expressing MDA-MB-231BR cells. Cell growth, EGFR pathways, and HPSE targets were assessed among selected clones in the absence or presence of Roneparstat and/or lapatinib. Roneparstat overcame lapatinib resistance by inhibiting pathways associated with EGFR tyrosine residues that are not targeted by lapatinib. Roneparstat inhibited the growth and BMBC abilities of lapatinib-resistant clones. A molecular mechanism was identified by which HPSE mediates an alternative survival pathway in lapatinib-resistant clones and is modulated by Roneparstat. These results demonstrate that the inhibition of HPSE-mediated signaling plays important roles in lapatinib resistance, and provide mechanistic insights to validate the use of Roneparstat for novel BMBC therapeutic strategies.
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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.