ArticleOncotarget2016
Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer.Frontiers in oncology · 2024Article
- REThinking the role of the RET oncogene in breast cancer.Frontiers in oncology · 2024Review
- RET signaling in breast cancer therapeutic resistance and metastasis.Breast cancer research : BCR · 2023Review
- A comprehensive overview of the relationship between RET gene and tumor occurrence.Frontiers in oncology · 2023Review
- AST-487 Inhibits RET Kinase Driven TERT Expression in Bladder Cancer.International journal of molecular sciences · 2022Article
- Pralsetinib: chemical and therapeutic development with FDA authorization for the management of RET fusion-positive non-small-cell lung cancers.Archives of pharmacal research · 2022Review
- RET signaling pathway and RET inhibitors in human cancer.Frontiers in oncology · 2022Review
- PredTAD: A machine learning framework that models 3D chromatin organization alterations leading to oncogene dysregulation in breast cancer cell lines.Computational and structural biotechnology journal · 2021Article
- Review
- Ret Receptor Has Distinct Alterations and Functions in Breast Cancer.Journal of mammary gland biology and neoplasia · 2020Review
- Significance of the Genomic Landscape of a De Novo Endocrine-Resistant Metastatic Hormone Receptor-Positive Breast Cancer.Breast cancer : basic and clinical research · 2020Article
- Expression of RET is associated with Oestrogen receptor expression but lacks prognostic significance in breast cancer.BMC cancer · 2019Article
- RET in breast cancer: pathogenic implications and mechanisms of drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- RET rearrangements are actionable alterations in breast cancer.Nature communications · 2018Article
- Application of a novel targeting nanoparticle contrast agent combined with magnetic resonance imaging in the diagnosis of intraductal papillary mucinous neoplasm.Experimental and therapeutic medicine · 2018Article
- GDNF and the RET Receptor in Cancer: New Insights and Therapeutic Potential.Frontiers in physiology · 2018Review
- The GDNF Family: A Role in Cancer?Neoplasia (New York, N.Y.) · 2018Review
- A bi-stable feedback loop between GDNF, EGR1, and ERα contribute to endocrine resistant breast cancer.PloS one · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The majority of breast cancers are estrogen receptor positive (ER+). Blockade of estrogen biosynthesis by aromatase inhibitors (AIs) is the first-line endocrine therapy for post-menopausal women with ER+ breast cancers. However, AI resistance remains a major challenge. We have demonstrated previously that increased GDNF/RET signaling in ER+ breast cancers promotes AI resistance. Here we investigated the efficacy of different small molecule RET kinase inhibitors, sunitinib, cabozantinib, NVP-BBT594 and NVP-AST487, and the potential of combining a RET inhibitor with the AI letrozole in ER+ breast cancers. The most effective inhibitor identified, NVP-AST487, suppressed GDNF-stimulated RET downstream signaling and 3D tumor spheroid growth. Ovariectomized mice were inoculated with ER+ aromatase-overexpressing MCF7-AROM1 cells and treated with letrozole, NVP-AST487 or the two drugs in combination. Surprisingly, the three treatment regimens showed similar efficacy in impairing MCF7-AROM1 tumor growth in vivo. However in vitro, NVP-AST487 was superior to letrozole in inhibiting the GDNF-induced motility and tumor spheroid growth of MCF7-AROM1 cells and required in combination with letrozole to inhibit GDNF-induced motility in BT474-AROM3 aromatase expressing cells. These data indicate that inhibiting RET is as effective as the current therapeutic regimen of AI therapy but that a combination treatment may delay cancer cell dissemination and metastasis.
Indexed as
Identifiers
What OpenQuestion holds
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.