ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2013
The role of p53 in combination radioimmunotherapy with 64Cu-DOTA-cetuximab and cisplatin in a mouse model of colorectal cancer.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 31 citations in OpenAlex.
- Review
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- Derivation and Clinical Validation of a Redox-Driven Prognostic Signature for Colorectal Cancer.Frontiers in oncology · 2021Article
- Cation Exchange Protocols to Radiolabel Aqueous Stabilized ZnS, ZnSe, and CuFeSAdvanced functional materials · 2020Article
- Biodistribution, pharmacokinetics and radioimmunotherapy ofInvestigational new drugs · 2019Article
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- Synthesis and evaluation ofChinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2019Article
- Combined external beam radiotherapy with carbon ions and tumor targeting endoradiotherapy.Oncotarget · 2018Article
- Integrated treatment using intraperitoneal radioimmunotherapy and positron emission tomography-guided surgery withOncotarget · 2018Article
- Targeted α-Particle Radiation Therapy of HER1-Positive Disseminated Intraperitoneal Disease: An Investigation of the Human Anti-EGFR Monoclonal Antibody, Panitumumab.Translational oncology · 2017Article
- Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer.Oncotarget · 2017Article
- Article
- Comparison of conjugation strategies of cross-bridged macrocyclic chelators with cetuximab for copper-64 radiolabeling and PET imaging of EGFR in colorectal tumor-bearing mice.Molecular pharmaceutics · 2014Article
- Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model.European journal of nuclear medicine and molecular imaging · 2014Article
- ⁶⁴Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer.Journal of medicinal chemistry · 2014Article
- Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy.Pharmaceuticals (Basel, Switzerland) · 2014Article
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5 authors at 3 institutions in 1 country.
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Abstract
unlabelledRadioimmunotherapy has been successfully used in the treatment of lymphoma but thus far has not demonstrated significant efficacy in humans beyond disease stabilization in solid tumors. Radioimmunotherapy with (64)Cu was highly effective in a hamster model of colorectal cancer, but targeted radiotherapies with this radionuclide have since not shown as much success. It is widely known that mutations in key proteins play a role in the success or failure of cancer therapies. For example, the KRAS mutation is predictive of poor response to anti-epidermal growth factor receptor therapies in colorectal cancer, whereas p53 is frequently mutated in tumors, causing resistance to multiple therapeutic regimens.
methodsWe previously showed that nuclear localization of (64)Cu-labeled DOTA-cetuximab was enhanced in p53 wild-type tumor cells. Here, we examine the role of p53 in the response to radioimmunotherapy with (64)Cu-DOTA-cetuximab in KRAS-mutated HCT116 tumor-bearing mice, with and without cisplatin, which upregulates wild-type p53.
resultsExperiments with HCT116 cells that are p53 +/+ (p53 wild-type) and -/- (p53 null) grown in cell culture demonstrated that preincubation with cisplatin increased expression of p53 and subsequently enhanced localization of (64)Cu from (64)Cu-acetate and (64)Cu-DOTA-cetuximab to the tumor cell nuclei. Radioimmunotherapy studies in p53-positive HCT116 tumor-bearing mice, receiving either radioimmunotherapy alone or in combination with cisplatin, showed significantly longer survival in mice receiving unlabeled cetuximab or cisplatin alone or in combination (all, P < 0.01). In contrast, the p53-negative tumor-bearing mice treated with radioimmunotherapy alone or combined with cisplatin showed no survival advantage, compared with control groups (all, P > 0.05).
conclusionTogether, these data suggest that (64)Cu specifically delivered to epidermal growth factor receptor-positive tumors by cetuximab can suppress tumor growth despite the KRAS status and present opportunities for personalized clinical treatment strategies in colorectal cancer.
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