ArticleCarcinogenesis2012
Sorafenib enhances the therapeutic efficacy of rapamycin in colorectal cancers harboring oncogenic KRAS and PIK3CA.
Article in Carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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
21 citing papers in PubMed, 27 citations in OpenAlex.
- Lipid Peroxidation in Cancer Therapy: Molecular Mechanisms Involving Oxidative Stress, Cell Death, and Therapeutic Response.Molecules (Basel, Switzerland) · 2026Review
- Impact of glucose metabolism on PD-L1 expression in sorafenib-resistant hepatocellular carcinoma cells.Scientific reports · 2024Article
- Sorafenib, rapamycin, and venetoclax attenuate doxorubicin-induced senescence and promote apoptosis in HCT116 cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Exploring the Anti-Cancer Mechanism of Novel 3,4'-Substituted Diaryl Guanidinium Derivatives.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Dual VEGF inhibition with sorafenib and bevacizumab as salvage therapy in metastatic colorectal cancer: results of the phase II North Central Cancer Treatment Group study N054C (Alliance).Therapeutic advances in medical oncology · 2020Article
- mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy.International journal of molecular sciences · 2019Review
- Combination of Everolimus with Sorafenib for Solid Renal Tumors in Tsc2Neoplasia (New York, N.Y.) · 2017Article
- Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.International journal of molecular sciences · 2016Article
- Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders.British journal of clinical pharmacology · 2016Review
- The mutational profile and infiltration pattern of murine MLH1-/- tumors: concurrences, disparities and cell line establishment for functional analysis.Oncotarget · 2016Article
- Modulation of Autophagy by Sorafenib: Effects on Treatment Response.Frontiers in pharmacology · 2016Review
- Establishment and characterization of cell lines from chromosomal instable colorectal cancer.World journal of gastroenterology · 2015Article
- Mammalian target of rapamycin complex 1 and cyclooxygenase 2 pathways cooperatively exacerbate endometrial cancer.The American journal of pathology · 2014Article
- BI-69A11 enhances susceptibility of colon cancer cells to mda-7/IL-24-induced growth inhibition by targeting Akt.British journal of cancer · 2014Article
- A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity.Cancer discovery · 2014Article
- Targeting mTOR network in colorectal cancer therapy.World journal of gastroenterology · 2014Review
- Caffeic acid derivatives inhibit the growth of colon cancer: involvement of the PI3-K/Akt and AMPK signaling pathways.PloS one · 2014Article
- Oncogenic mutations and microsatellite instability phenotype predict specific anatomical subsite in colorectal cancer patients.European journal of human genetics : EJHG · 2013Article
- Off-label use of cetuximab plus sorafenib and panitumumab plus regorafenib to personalize therapy for a patient with V600E BRAF-mutant metastatic colon cancer.Cancer biology & therapy · 2013Article
- Deregulation of Wnt/β-catenin signaling through genetic or epigenetic alterations in human neuroendocrine tumors.Carcinogenesis · 2013Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling is associated with tumorigenesis and metastasis of colorectal cancer (CRC). The mammalian target of rapamycin (mTOR) kinase, a downstream effector of PI3K/Akt signaling, regulates tumorigenesis and metastasis of CRCs, indicating that mTOR inhibition may have therapeutic potential. Notwithstanding, many cancers, including CRC, demonstrate resistance to the antitumorigenic effects of rapamycin. In this study, we show that inhibition of mTORC1 with rapamycin leads to feedback activation of PI3K/Akt and Ras-MAPK signaling, resulting in cell survival and possible contribution to rapamycin resistance. Combination with the multikinase inhibitor, sorafenib, abrogates rapamycin-induced activation of PI3K/Akt and Ras-MAPK signaling pathways. Combination of rapamycin with sorafenib synergistically inhibits proliferation of CRC cells. CRCs harboring coexistent KRAS and PIK3CA mutations are partially sensitive to either rapamycin or sorafenib monotherapy, but highly sensitive to combination treatment with rapamycin and sorafenib. Combination with sorafenib enhances therapeutic efficacy of rapamycin on induction of apoptosis and inhibition of cell-cycle progression, migration and invasion of CRCs. We demonstrate efficacy and safety of concomitant treatment with rapamycin and sorafenib at inhibiting growth of xenografts from CRC cells with coexistent mutations in KRAS and PIK3CA. The efficacy and tolerability of combined treatment with rapamycin and sorafenib provides rationale for use in treating CRC patients, particularly those with tumors harboring coexistent KRAS and PIK3CA mutations.
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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.