ReviewCancers2024
Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer.
Review in Cancers, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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
34 citing papers in PubMed.
- Targeting the Chromatin-Modifying Enzyme, KDM5C, Enhances AKT Inhibition Response in ER+ Breast Cancer.Molecular cancer therapeutics · 2026Article
- Recent advances in hormone-based biopharmaceuticals for cancer therapy.Journal of the Egyptian National Cancer Institute · 2026Review
- Emerging Strategies Targeting the PI3K/AKT/mTOR Pathway in HR+/HER2- Advanced Breast Cancer.Drugs · 2026Review
- Genetic Ablation and Multi-Omics Profiling Reveal CEP55 as a Key Driver of Tumorigenesis in Diverse Cancer Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overcoming mTOR Inhibitor Resistance: From Biological Basis to Therapeutic Strategies.Biomedicines · 2026Review
- Breast Cancer: Epidemiology, Molecular Classification, Diagnostics and Evolving Treatment Paradigms.Molecules (Basel, Switzerland) · 2026Review
- Cancer signaling networks in tumor progression and drug resistance: Crosstalk, adaptive reprogramming and therapeutic targeting (Review).Oncology reports · 2026Review
- Rewiring mTOR signaling in Alzheimer's disease: emerging mTOR modulators beyond oncology.Bioscience reports · 2026Review
- Dehydrocorydaline Exerts Anti-Pancreatic Cancer Effects Through the PI3K/Akt/mTOR Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Molecular mechanisms and therapeutic targeting implications of ER/mTOR signaling axis-driven tumor progression in aggressive meningiomas.Translational oncology · 2026Article
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- A Darwinian Perspective on Tumor Evolution.International journal of biological sciences · 2026Review
- Progress for RAD18's mechanism in breast cancer radioresistant.Open life sciences · 2026Review
- Core Acupoint Prescription Patterns for Primary Dysmenorrhea: Data Mining and Network-Based Analysis.Journal of pain research · 2026Article
- Precision oncology in gynecologic cancers: molecular taxonomy, biomarker-guided therapeutics, and the challenge of therapeutic resistance.Frontiers in oncology · 2026Review
- Decoding Breast Cancer: Emerging Molecular Biomarkers and Novel Therapeutic Targets for Precision Medicine.International journal of molecular sciences · 2025Review
- Meta-Analysis and Experimental Studies Reveal Mitotic Network Activity Index (MNAI) as Breast Cancer Metastasis and Treatment Biomarker.Life (Basel, Switzerland) · 2025Article
- Innovative theranostic potential of graphene quantum dot nanocomposites in breast cancer.Medical oncology (Northwood, London, England) · 2025Review
- Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PI3K/AKT/mTOR signalling pathway is one of the most frequently activated pathways in breast cancer and also plays a central role in the regulation of several physiologic functions. There are major efforts ongoing to exploit precision medicine by developing inhibitors that target the three kinases (PI3K, AKT, and mTOR). Although multiple compounds have been developed, at present, there are just three inhibitors approved to target this pathway in patients with advanced ER-positive, HER2-negative breast cancer: everolimus (mTOR inhibitor), alpelisib (PIK3CA inhibitor), and capivasertib (AKT inhibitor). Like most targeted cancer drugs, resistance poses a major problem in the clinical setting and is a factor that has frequently limited the overall efficacy of these agents. Drug resistance can be categorised into intrinsic or acquired resistance depending on the timeframe it has developed within. Whereas intrinsic resistance exists prior to a specific treatment, acquired resistance is induced by a therapy. The majority of patients with ER-positive, HER2-negative advanced breast cancer will likely be offered an inhibitor of the PI3K/AKT/mTOR pathway at some point in their cancer journey, with the options available depending on the approval criteria in place and the cancer's mutation status. Within this large cohort of patients, it is likely that most will develop resistance at some point, which makes this an area of interest and an unmet need at present. Herein, we review the common mechanisms of resistance to agents that target the PI3K/AKT/mTOR signalling pathway, elaborate on current management approaches, and discuss ongoing clinical trials attempting to mitigate this significant issue. We highlight the need for additional studies into AKT1 inhibitor resistance in particular.
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