Cancer letters, 2019-03, Vol.444, p.147-161
2019
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Details
- Autor(en) / Beteiligte
- Titel
- Modulation of lung cancer cell plasticity and heterogeneity with the restoration of cisplatin sensitivity by neurotensin antibody
- Ist Teil von
- Cancer letters, 2019-03, Vol.444, p.147-161
- Ort / Verlag
- Ireland: Elsevier B.V
- Erscheinungsjahr
- 2019
- Quelle
- Alma/SFX Local Collection
- Beschreibungen/Notizen
- Overall survival of patients with metastatic non-small cell lung cancer (NSCLC) has significantly improved with platinum-based salt treatments and recently with targeted therapies and immunotherapies. However, treatment failure occurs due to acquired or emerging tumor resistance. We developed a monoclonal antibody against the proform of neurotensin (LF-NTS mAb) that alters the homeostasis of tumors overexpressing NTSR1. Neurotensin is frequently overexpressed along with its high affinity receptor (NTSR1) in tumors from epithelial origins. This ligand/receptor complex contributes to the progression of many tumor types by activation of the cellular effects involved in tumor progression (proliferation, survival, migration, and invasion). We demonstrate that LF-NTS mAb operates on the plasticity of tumor cells overexpressing NTSR1 and lowers their aggressiveness. The mAb enables the restoration of platinum-based therapies responsiveness, while also decreasing metastatic processes. Efficacy dosage with long-term treatment showed no obvious adverse events, while demonstrating improvement in the performance status. Our data suggests that LF-NTS mAb is an ideal candidate to be safely added to the conventional standard of care in order to improve its efficacy. •Neurotensin targeted therapy decreases tumor growth and metastasis processes, while restoring drug responsiveness.•Neurotensin targeted therapy creates no additional toxicity.•Neurotensin targeted therapy improves performance status.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0304-3835eISSN: 1872-7980DOI: 10.1016/j.canlet.2018.12.007Titel-ID: cdi_swepub_primary_oai_lup_lub_lu_se_0ccee0f0_49b3_4ea5_92f8_6eeb7b019149
- Format
- –
- Schlagworte
- Advanced lung cancer, Aggressiveness, Anti-tumor drug, Apoptosis, Brain tumors, Cancer, Cancer and Oncology, Cancer och onkologi, Cancer therapies, Cell survival, Chemotherapy, Cisplatin, Clinical Medicine, Cloning, Deoxyribonucleic acid, DNA, Epidermal growth factor, Heterogeneity, Homeostasis, Immunotherapy, Kinases, Klinisk medicin, Life Sciences, Lung cancer, Lymphoma, Medical and Health Sciences, Medicin och hälsovetenskap, Metastases, Metastasis, Migration, Monoclonal antibodies, Mutation, Neurotensin, Neurotensin antibody, Non-small cell lung carcinoma, Patients, Plastic properties, Plasticity, Platinum, Proteins, Restoration of platinum salt-based chemotherapy sensitivity, Solitary tract nucleus, Tumor cell plasticity, Tumor cells, Tumors