ArticleEndocrine-related cancer2019
PI3K/mTOR inhibition potentiates and extends palbociclib activity in anaplastic thyroid cancer.
Article in Endocrine-related cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2021Guideline
- Convergent Mechanistic Pathways Driving the Anaplastic Phenotype in Thyroid Cancer.International journal of molecular sciences · 2026Review
- The Role of Kinase Inhibitors in Cancer Neuroscience: Mechanisms, Therapeutic Potential, and Future Directions.Anti-cancer agents in medicinal chemistry · 2026Review
- Targeted therapy in thyroid cancer: molecular alterations and clinical management.Frontiers in endocrinology · 2026Review
- Article
- Post-translational modifications in anaplastic thyroid carcinoma: biological mechanisms and therapeutic potential.Cancer cell international · 2025Review
- Extracellular vesicle-associated transcriptomic and proteomic biomarkers show in vitro potential for vandetanib treatment monitoring in anaplastic thyroid cancer.Scientific reports · 2025Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Differential activity of specific inhibitors of transcription regulating cyclin-dependent kinases in thyroid cancer cells.Endocrine-related cancer · 2025Article
- New Horizons of Biomarkers in Metastatic Thyroid Cancer.Journal of Cancer · 2025Review
- Benzyl isothiocyanate suppresses development of thyroid carcinoma by regulating both autophagy and apoptosis pathway.iScience · 2024Article
- A zebrafish xenotransplant model of anaplastic thyroid cancer to study tumor microenvironment and innate immune cell interactions in vivo.Endocrine-related cancer · 2024Article
- Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.Molecular oncology · 2024Article
- Lysicamine Reduces Protein Kinase B (AKT) Activation and Promotes Necrosis in Anaplastic Thyroid Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Anti-leukemia effects of omipalisib in acute myeloid leukemia: inhibition of PI3K/AKT/mTOR signaling and suppression of mitochondrial biogenesis.Cancer gene therapy · 2023Article
- Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The effects of Abemaciclib on cell cycle and apoptosis regulation in anaplastic thyroid cancer cells.Molecular biology reports · 2023Article
- Multi-Omics and Management of Follicular Carcinoma of the Thyroid.Biomedicines · 2023Review
- Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas.Cancers · 2023Article
- CDK4 phosphorylation status and rational use for combining CDK4/6 and BRAF/MEK inhibition in advanced thyroid carcinomas.Frontiers in endocrinology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer. Despite its low incidence, it accounts for a disproportionate number of thyroid cancer-related deaths, because of its resistance to current therapeutic approaches. Novel actionable targets are urgently needed to prolong patient survival and increase their quality of life. Loss and mutation of the RB1 tumor suppressor are rare events in ATC, which suggests that therapies directed at inhibiting the cyclin D/CDK4 complexes, responsible for RB phosphorylation and inactivation, might be effective in this tumor type. In fact, we found that the CDK4/6 inhibitor, palbociclib, strongly inhibits proliferation in all the RB1 wild type ATC cell lines tested. Efficacy was also observed in vivo, in a xenograft model. However, ATC cells rapidly developed resistance to palbociclib. Resistance was associated with increased levels of cyclin D1 and D3. To counter cyclin D overexpression, we tested the effect of combining palbociclib with the PI3K/mTOR dual inhibitor, omipalisib. Combined treatment synergistically reduced cell proliferation, even in cell lines that do not carry PI3K-activating mutations. More importantly, low-dose combination was dramatically effective in inhibiting tumor growth in a xenograft model. Thus, combined PI3K/mTOR and CDK4/6 inhibition is a highly promising novel approach for the treatment of aggressive, therapy-resistant thyroid cancer.
Indexed as
Identifiers
What Socratic 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 Socratic graph.