Literature DB >> 27279153

The applications of the novel polymeric fluoropyrimidine F10 in cancer treatment: current evidence.

William H Gmeiner1,2, Waldemar Debinski1,2,3, Carol Milligan1,4, David Caudell1,5, Timothy S Pardee1,2,6.   

Abstract

F10 is a novel polymeric fluoropyrimidine drug candidate with strong anticancer activity in multiple preclinical models. F10 has strong potential for impacting cancer treatment because it displays high cytotoxicity toward proliferating malignant cells with minimal systemic toxicities thus providing an improved therapeutic window relative to traditional fluoropyrimidine drugs, such as 5-fluorouracil. F10 has a unique mechanism that involves dual targeting of thymidylate synthase and Top1. In this review, the authors provide an overview of the studies that revealed the novel aspects of F10's cytotoxic mechanism and summarize results obtained in preclinical models of acute myeloid leukemia, acute lymphocytic leukemia, glioblastoma and prostate cancer that demonstrate the strong potential of F10 to improve treatment outcomes.

Entities:  

Keywords:  acute leukemia; cancer chemotherapy; fluoropyrimidine; glioblastoma; prostate cancer; thymineless death; topoisomerase

Mesh:

Substances:

Year:  2016        PMID: 27279153      PMCID: PMC4992963          DOI: 10.2217/fon-2016-0091

Source DB:  PubMed          Journal:  Future Oncol        ISSN: 1479-6694            Impact factor:   3.404


  65 in total

1.  A novel polypyrimidine antitumor agent FdUMP[10] induces thymineless death with topoisomerase I-DNA complexes.

Authors:  Zhi-Yong Liao; Olivier Sordet; Hong-Liang Zhang; Glenda Kohlhagen; Smitha Antony; William H Gmeiner; Yves Pommier
Journal:  Cancer Res       Date:  2005-06-01       Impact factor: 12.701

2.  Effect of the thymidylate synthase inhibitors on dUTP and TTP pool levels and the activities of DNA repair glycosylases on uracil and 5-fluorouracil in DNA.

Authors:  Breeana C Grogan; Jared B Parker; Amy F Guminski; James T Stivers
Journal:  Biochemistry       Date:  2011-01-11       Impact factor: 3.162

3.  Unique dual targeting of thymidylate synthase and topoisomerase1 by FdUMP[10] results in high efficacy against AML and low toxicity.

Authors:  Timothy S Pardee; Evan Gomes; Jamie Jennings-Gee; David Caudell; William H Gmeiner
Journal:  Blood       Date:  2012-02-23       Impact factor: 22.113

Review 4.  The NCI60 human tumour cell line anticancer drug screen.

Authors:  Robert H Shoemaker
Journal:  Nat Rev Cancer       Date:  2006-10       Impact factor: 60.716

Review 5.  Topoisomerase I inhibitors: camptothecins and beyond.

Authors:  Yves Pommier
Journal:  Nat Rev Cancer       Date:  2006-10       Impact factor: 60.716

6.  Transcription-dependent degradation of topoisomerase I-DNA covalent complexes.

Authors:  Shyamal D Desai; Hui Zhang; Alexandra Rodriguez-Bauman; Jin-Ming Yang; Xiaohua Wu; Murugesan K Gounder; Eric H Rubin; Leroy F Liu
Journal:  Mol Cell Biol       Date:  2003-04       Impact factor: 4.272

7.  Cytarabine with high-dose mitoxantrone induces rapid complete remissions in adult acute lymphoblastic leukemia without the use of vincristine or prednisone.

Authors:  M Weiss; P Maslak; E Feldman; E Berman; J Bertino; T Gee; L Megherian; K Seiter; D Scheinberg; D Golde
Journal:  J Clin Oncol       Date:  1996-09       Impact factor: 44.544

8.  Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.

Authors:  Ian F Tannock; Ronald de Wit; William R Berry; Jozsef Horti; Anna Pluzanska; Kim N Chi; Stephane Oudard; Christine Théodore; Nicholas D James; Ingela Turesson; Mark A Rosenthal; Mario A Eisenberger
Journal:  N Engl J Med       Date:  2004-10-07       Impact factor: 91.245

9.  Mechanisms of action of FdUMP[10]: metabolite activation and thymidylate synthase inhibition.

Authors:  I V Bijnsdorp; E M Comijn; J M Padron; W H Gmeiner; G J Peters
Journal:  Oncol Rep       Date:  2007-07       Impact factor: 3.906

10.  Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer.

Authors:  M Gusella; A C Frigo; C Bolzonella; R Marinelli; C Barile; A Bononi; G Crepaldi; D Menon; L Stievano; S Toso; F Pasini; E Ferrazzi; R Padrini
Journal:  Br J Cancer       Date:  2009-04-21       Impact factor: 7.640

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  12 in total

1.  All-atom MD indicates ion-dependent behavior of therapeutic DNA polymer.

Authors:  Ryan L Melvin; William H Gmeiner; Freddie R Salsbury
Journal:  Phys Chem Chem Phys       Date:  2017-08-23       Impact factor: 3.676

Review 2.  F10 cytotoxicity via topoisomerase I cleavage complex repair consistent with a unique mechanism for thymineless death.

Authors:  William H Gmeiner; Patricia J Gearhart; Yves Pommier; Jun Nakamura
Journal:  Future Oncol       Date:  2016-06-22       Impact factor: 3.404

3.  All-Atom Molecular Dynamics Reveals Mechanism of Zinc Complexation with Therapeutic F10.

Authors:  Ryan L Melvin; William H Gmeiner; Freddie R Salsbury
Journal:  J Phys Chem B       Date:  2016-09-21       Impact factor: 2.991

4.  Development of a Colorectal Cancer 3D Micro-tumor Construct Platform From Cell Lines and Patient Tumor Biospecimens for Standard-of-Care and Experimental Drug Screening.

Authors:  Steven Forsythe; Naren Mehta; Mahesh Devarasetty; Hemamylammal Sivakumar; William Gmeiner; Shay Soker; Konstantinos Votanopoulos; Aleksander Skardal
Journal:  Ann Biomed Eng       Date:  2019-04-24       Impact factor: 3.934

5.  Floxuridine Homomeric Oligonucleotides "Hitchhike" with Albumin In Situ for Cancer Chemotherapy.

Authors:  Cheng Jin; Hui Zhang; Jianmei Zou; Yan Liu; Lin Zhang; Fengjie Li; Ruowen Wang; Wenjing Xuan; Mao Ye; Weihong Tan
Journal:  Angew Chem Int Ed Engl       Date:  2018-06-19       Impact factor: 15.336

6.  Enhancing Antitumor Efficacy of Nucleoside Analog 5-Fluorodeoxyuridine on HER2-Overexpressing Breast Cancer by Affibody-Engineered DNA Nanoparticle.

Authors:  Chao Zhang; Mengnan Han; Fanghua Zhang; Xueli Yang; Jie Du; Honglei Zhang; Wei Li; Shengxi Chen
Journal:  Int J Nanomedicine       Date:  2020-02-10

7.  AraC-FdUMP[10] Is a Next-Generation Fluoropyrimidine with Potent Antitumor Activity in PDAC and Synergy with PARG Inhibition.

Authors:  William H Gmeiner; Jonathan R Brody; Alex O Haber; Aditi Jain; Chinnadurai Mani; Avinoam Nevler; Lebaron C Agostini; Talia Golan; Komaraiah Palle; Charles J Yeo
Journal:  Mol Cancer Res       Date:  2021-02-16       Impact factor: 6.333

8.  Thymineless Death by the Fluoropyrimidine Polymer F10 Involves Replication Fork Collapse and Is Enhanced by Chk1 Inhibition.

Authors:  Chinnadurai Mani; Sachin Pai; Cinta Maria Papke; Komaraiah Palle; William H Gmeiner
Journal:  Neoplasia       Date:  2018-11-12       Impact factor: 5.715

9.  Improved potency of F10 relative to 5-fluorouracil in colorectal cancer cells with p53 mutations.

Authors:  Anthony Dominijanni; William H Gmeiner
Journal:  Cancer Drug Resist       Date:  2018-03-19

10.  Dysregulated Pyrimidine Biosynthesis Contributes to 5-FU Resistance in SCLC Patient-Derived Organoids but Response to a Novel Polymeric Fluoropyrimidine, CF10.

Authors:  William H Gmeiner; Lance D Miller; Jeff W Chou; Anthony Dominijanni; Lysette Mutkus; Frank Marini; Jimmy Ruiz; Travis Dotson; Karl W Thomas; Graham Parks; Christina R Bellinger
Journal:  Cancers (Basel)       Date:  2020-03-26       Impact factor: 6.639

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