ReviewOncotarget2012
Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance.
Review in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 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
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 315 citations in OpenAlex.
- A meta-analysis approach for characterizing pan-cancer mechanisms of drug sensitivity in cell lines.PloS one · 2014Pooled it
- Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.Journal of experimental & clinical cancer research : CR · 2026Review
- A case report of neoadjuvant targeted therapy in stage IIIA non-small cell lung cancer withFrontiers in medicine · 2025Article
- mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors.Cancer research communications · 2024Article
- Inhibition of Liver Cancer Cell Viability by Triazole through Up-regulation of p38 Phosphorylation and Targeting the Activation of p-ERK1/2 and Akt Protein Expression.Doklady. Biochemistry and biophysics · 2024Article
- BCL-2 inhibitors in hematological malignancies: biomarkers that predict response and management strategies.Frontiers in oncology · 2024Review
- Decoding the anti-cancer potential of Pexidartinib (PLX3397), a Fms-like tyrosine kinase 3 inhibitor, using next-generation knowledge discovery methods.Bioinformation · 2024Article
- Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management.International journal of molecular sciences · 2023Review
- Prolonged Inhibition of the MEK1/2-ERK Signaling Axis Primes Interleukin-1 Beta Expression through Histone 3 Lysine 9 Demethylation in Murine Macrophages.International journal of molecular sciences · 2023Article
- Hepatocellular Carcinoma cells: activity of Amygdalin and Sorafenib in Targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death.BMC complementary medicine and therapies · 2023Article
- Therapeutic Targeting of Regulated Signaling Pathways of Non-Small Cell Lung Carcinoma.ACS omega · 2023Review
- Ran GTPase and Its Importance in Cellular Signaling and Malignant Phenotype.International journal of molecular sciences · 2023Review
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Genetic features and therapeutic relevance of emergent circulating tumor DNA alterations in refractory non-colorectal gastrointestinal cancers.Nature communications · 2022Article
- Targeted activation of ERK1/2 reduces ischemia and reperfusion injury in hyperglycemic myocardium by improving mitochondrial function.Annals of translational medicine · 2022Article
- Pathological Role of HDAC8: Cancer and Beyond.Cells · 2022Review
- Simultaneous Imaging and Therapy Using Epitope-Specific Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Conjugates.Pharmaceutics · 2022Article
- AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to killHaematologica · 2022Article
- Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.International journal of molecular sciences · 2022Review
- Ipatasertib, an oral AKT inhibitor, inhibits cell proliferation and migration, and induces apoptosis in serous endometrial cancer.American journal of cancer research · 2022Article
118 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have been investigated in pre-clinical and clinical investigations and then discuss how cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance.
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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.