ArticleAutophagy2017
Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Pooled it
- Advances in endometrial cancer screening: a comprehensive review of current methods and emerging technologies.International journal of clinical oncology · 2026Review
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- Dynamics of autophagy in response to high linear energy transfer radiation and cancer.Korean journal of clinical oncology · 2025Review
- Targeting CXCR6 Disrupts β-Catenin Signaling and Enhances Sorafenib Response in Hepatocellular Carcinoma.Cancers · 2025Article
- Metabolomics reveals the therapeutic efficacy of liposomal resvida in endometrial cancer through regulating autophagy-related gene expression.Cancer cell international · 2025Article
- Autophagy in cancer and protein conformational disorders.FEBS letters · 2025Review
- The role of the pathologist in the design and conducting of biomarker-driven clinical trials in cancer: position paper of the European Society of Pathology.Virchows Archiv : an international journal of pathology · 2025Review
- Inflammation-driven mechanisms in endometrial cancer: pathways from inflammatory microenvironment remodeling to immune escape.Frontiers in immunology · 2025Review
- Inhibition of autophagy enhances the sensitivity of ciclopirox olamine in human chronic myelogenous leukemia K562 cells.International journal of medical sciences · 2025Article
- Review
- Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.International journal of molecular sciences · 2024Article
- Advances in research on autophagy mechanisms in resistance to endometrial cancer treatment.Frontiers in oncology · 2024Review
- RBFOX2 as a regulatory linchpin in cancer: insights from a comprehensive review of its roles in tumorigenesis.American journal of cancer research · 2024Review
- The Roles of Autophagy-related miRNAs in Gynecologic Tumors: A Review of Current Knowledge for Possible Targeted Therapy.Current molecular medicine · 2024Review
- Oxidative stress-induced FAK activation contributes to uterine serous carcinoma aggressiveness.Molecular oncology · 2023Article
- The use of African medicinal plants in cancer management.Frontiers in pharmacology · 2023Review
- MLLT11-TRIL complex promotes the progression of endometrial cancer through PI3K/AKT/mTOR signaling pathway.Cancer biology & therapy · 2022Article
- Generation and Integrated Analysis of Advanced Patient-Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- An eleven autophagy-related genes-based prognostic signature for endometrial carcinoma.Journal of the Egyptian National Cancer Institute · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma. Unfortunately, sorafenib showed very modest effects in a multi-institutional phase II trial in advanced uterine carcinoma patients. Here, by leveraging RNA-sequencing data from the Cancer Cell Line Encyclopedia and cell survival studies from compound-based high-throughput screenings we have identified the lysosomal pathway as a potential compartment involved in the resistance to sorafenib. By performing additional functional biology studies we have demonstrated that this resistance could be related to macroautophagy/autophagy. Specifically, our results indicate that sorafenib triggers a mechanistic MAPK/JNK-dependent early protective autophagic response in EC cells, providing an adaptive response to therapeutic stress. By generating in vivo subcutaneous EC cell line tumors, lung metastatic assays and primary EC orthoxenografts experiments, we demonstrate that targeting autophagy enhances sorafenib cytotoxicity and suppresses tumor growth and pulmonary metastasis progression. In conclusion, sorafenib induces the activation of a protective autophagic response in EC cells. These results provide insights into the unopposed resistance of advanced EC to sorafenib and highlight a new strategy for therapeutic intervention in recurrent EC.
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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.