ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Regorafenib inhibits colorectal tumor growth through PUMA-mediated apoptosis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Long non-coding PANDAR as a novel biomarker in human cancer: A systematic review.Cell proliferation · 2018Pooled it
- Trial
- Targeting WRN Helicase in Microsatellite-Instable Colorectal Cancer Induces Antitumor Immunity through Extrachromosomal Circular DNA Release.Cancer research · 2026Article
- Reactivating necroptosis in colorectal cancer potentiates chemotherapy and antitumor immune responses.Cancer letters · 2026Article
- Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy.Cell death and differentiation · 2025Article
- Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy.Current treatment options in oncology · 2025Review
- Regorafenib with or without chemotherapy/immunotherapy in second-line treatment of metastatic colorectal cancer during the COVID-19 pandemic: a single-center retrospective analysis.Journal of gastrointestinal oncology · 2024Article
- Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo.BMC cancer · 2024Article
- Article
- PUMA/RIP3 Mediates Chemotherapy Response via Necroptosis and Local Immune Activation in Colorectal Cancer.Molecular cancer therapeutics · 2024Article
- Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation.Cancer research communications · 2024Article
- Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams.Cancers · 2023Review
- Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.Nature communications · 2023Article
- The sodium channel subunit SCNN1B suppresses colorectal cancer via suppression of active c-Raf and MAPK signaling cascade.Oncogene · 2023Article
- Regorafenib induces Bim-mediated intrinsic apoptosis by blocking AKT-mediated FOXO3a nuclear export.Cell death discovery · 2023Article
- Chemo-radiotherapy withFrontiers in medicine · 2023Article
- Synergistic antitumor activity of regorafenib and rosuvastatin in colorectal cancer.Frontiers in pharmacology · 2023Article
- Inhibition of the PINK1-Parkin Pathway Enhances the Lethality of Sorafenib and Regorafenib in Hepatocellular Carcinoma.Frontiers in pharmacology · 2022Article
- Dual inhibition of BET and HAT/p300 suppresses colorectal cancer via DR5- and p53/PUMA-mediated cell death.Frontiers in oncology · 2022Article
- Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeRegorafenib, a multikinase inhibitor targeting the Ras/Raf/MEK/ERK pathway, has recently been approved for the treatment of metastatic colorectal cancer. However, the mechanisms of action of regorafenib in colorectal cancer cells have been unclear. We investigated how regorafenib suppresses colorectal cancer cell growth and potentiates effects of other chemotherapeutic drugs. EXPERIMENTAL
designWe determined whether and how regorafenib induces the expression of PUMA, a p53 target and a critical mediator of apoptosis in colorectal cancer cells. We also investigated whether PUMA is necessary for the killing and chemosensitization effects of regorafenib in colorectal cancer cells. Furthermore, xenograft tumors were used to test if PUMA mediates the in vivo antitumor, antiangiogenic, and chemosensitization effects of regorafenib.
resultsWe found that regorafenib treatment induces PUMA in colorectal cancer cells irrespective of p53 status through the NF-κB pathway following ERK inhibition and glycogen synthase kinase 3β activation. Upregulation of PUMA is correlated with apoptosis induction in different colorectal cancer cell lines. PUMA is necessary for regorafenib-induced apoptosis in colorectal cancer cells. Chemosensitization by regorafenib is mediated by enhanced PUMA induction through different pathways. Furthermore, deficiency in PUMA abrogates the in vivo antitumor, antiangiogenic, and chemosensitization effects of regorafenib.
conclusionsOur results demonstrate a key role of PUMA in mediating the anticancer effects of regorafenib in colorectal cancer cells. They suggest that PUMA induction can be used as an indicator of regorafenib sensitivity, and also provide a rationale for manipulating the apoptotic machinery to improve the therapeutic efficacy of regorafenib and other targeted drugs.
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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.