Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
September-2021 Volume 15 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2021 Volume 15 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Case Report Open Access

Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review

  • Authors:
    • Michael A. Morse
    • Sant P. Chawla
    • Terence Z. Wong
    • Howard W. Bruckner
    • Frederick L. Hall
    • Erlinda M. Gordon
  • View Affiliations / Copyright

    Affiliations: Medical Oncology, Duke University Medical Center, Durham, NC 27710, USA, Cancer Center of Southern California, Santa Monica, CA 90403, USA, Bruckner Oncology, Bronx, NY 10469, USA, Delta Next‑Gene, LLC, Santa Monica, CA 90405, USA
    Copyright: © Morse et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 186
    |
    Published online on: July 8, 2021
       https://doi.org/10.3892/mco.2021.2348
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

DeltaRex‑G is a replication‑incompetent amphotropic murine leukemia virus‑based retroviral vector that displays a collagen‑matrix‑targeting decapeptide on its surface envelope protein, gp70, and encodes a cytocidal ‘dominant negative’, i.e. a truncated construct of the executive cyclin G1 (CCNG1) oncogene. DeltaRex-G inhibits the CCNG1 function of promoting cell competence and survival through the commanding CCNG1/cyclin‑dependent kinase (CDK)/Myc/mouse double minute 2 homolog (Mdm2)/p53 axis. In 2009, DeltaRex-G was granted Fast Track designation from the US Food and Drug Administration for the treatment of pancreatic cancer. In 2019, the results of a phase 1/2 study that used DeltaRex-G as monotherapy for stage 4 chemotherapy-resistant pancreatic ductal adenocarcinoma (PDAC) were published. A unique participant of the aforementioned phase 1/2 study is now an 84‑year‑old Caucasian woman with chemoresistant PDAC who was treated with DeltaRex‑G, 3x1011 colony forming units (cfu)/dose, 3 times/week for 4 weeks with a 2‑week rest period, for 1.5 years. During the treatment period, the patient's tumors in the liver, lymph node and peritoneum exhibited progressive decreases in size, which were accompanied by a reduction and normalization of serum carbohydrate antigen 19‑9 levels, and the patient achieved complete remission after 8 months of DeltaRex‑G therapy with minimal side effects (grade 2 fatigue). Henceforth, the patient has been in remission for 12 years with no evidence of disease, no late therapy‑related adverse events, and no further cancer therapy following DeltaRex‑G treatment. The present study reports a mutation of tumor protein p53 (TP53) (G199V) found retrospectively in the patient's archived tumor samples. TP53 is a well‑characterized tumor suppressor gene, and a critical regulatory component of the executive CCNG1/CDK/Myc/Mdm2/p53 axis, which regulates proliferative cell competence, DNA fidelity and survival. Studies are underway to determine whether TP53 mutations in pancreatic cancer can help identify a subset of patients with advanced metastatic cancer with an otherwise poor prognosis who would respond favorably to DeltaRex‑G, which would broaden the treatment options for patients with otherwise lethal PDAC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

American Cancer Society: Survival Rates for Pancreatic Cancer. American Cancer Society. https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html. Acessed February 12, 2021.

2 

Malone ER, Oliva M, Sabatini PJB, Stockley TL and Siu LL: Molecular profiling for precision cancer therapies. Genome Med. 12(8)2020.PubMed/NCBI View Article : Google Scholar

3 

Von Hoff DD, Ervin T, Arena FP, Chiorean G, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus Gemcitabine. N Engl J Med. 369:1691–1703. 2013.PubMed/NCBI View Article : Google Scholar

4 

Chawla SP, Bruckner H, Morse MA, Assudani N, Hall FL and Gordon EM: A phase I/II clinical study on the safety, efficacy, and therapeutic potential of intravenous DeltaRex-G: A tumor-targeted retrovector encoding a dominant-negative cyclin G1 inhibitor for advanced pancreatic cancer. Mol Ther Oncol. 12:56–67. 2019.PubMed/NCBI View Article : Google Scholar

5 

Al-Shihabi A, Chawla SP, Hall FL and Gordon EM: Exploiting oncogenic drivers along the CCNG1 pathway for cancer therapy and gene therapy. Mol Ther Oncolytics. 11:122–126. 2018.PubMed/NCBI View Article : Google Scholar

6 

Esfahani MS, Lee LJ, Jeon YJ, Flynn RA, Stehr H, Hui AB, Ishisoko N, Kildebeck E, Newman AM, Bratman SV, et al: Functional significance of U2AF1 S34F mutations in lung adenocarcinomas. Nat Commun. 10(5712)2019.PubMed/NCBI View Article : Google Scholar

7 

Cicenas J, Kvederaviciute K, Meskinyte I, Meskinyte-Kausiliene E, Skeberdyte A and Cicenas J: KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 mutations in pancreatic cancer. Cancers (Basel). 9(42)2017.PubMed/NCBI View Article : Google Scholar

8 

Kimura SH and Nojima H: Cyclin G1 associates with MDM2 and regulates accumulation and degradation of p53 protein. Genes Cells. 7:869–880. 2002.PubMed/NCBI View Article : Google Scholar

9 

Giono LE and Manfredim JJ: The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cell Physiol. 209:13–20. 2006.PubMed/NCBI View Article : Google Scholar

10 

Gordon EM, Ravicz JR, Liu S, Chawla SP and Hall FL: Cell cycle checkpoint control: The cyclin G1/Mdm2/p53 axis emerges as a strategic target for broad-spectrum cancer gene therapy-a review of molecular mechanisms for oncologists. Mol Clin Oncol. 9:115–134. 2018.PubMed/NCBI View Article : Google Scholar

11 

Chen X: Cyclin G: A regulator of the p53-Mdm2 network. Dev Cell. 2:518–519. 2002.PubMed/NCBI View Article : Google Scholar

12 

Jensen MR, Factor VM, Fantozzi A, Helin K, Huh CG and Thorgeirsson SS: Reduced hepatic tumor incidence in Cyclin G1-deficient mice. Hepatology. 37:862–870. 2003.PubMed/NCBI View Article : Google Scholar

13 

Olivier M, Hollstein M and Hainau P: TP53 mutations in human cancers: Origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2(a001008)2010.PubMed/NCBI View Article : Google Scholar

14 

Gordon EM, Liu PX, Chen ZH, Liu L, Whitley MD, Gee C, Groshen S, Hinton DR, Beart RW and Hall FL: Inhibition of metastatic tumor growth in nude mice by portal vein infusions of matrix-targeted retroviral vectors bearing a cytocidal cyclin G1 construct. Cancer Res. 60:3343–3347. 2000.PubMed/NCBI

15 

Gordon EM, Chen ZH, Liu L, Whitley M, Liu L, Wei D, Groshen S, Hinton DR, Anderson WF, Beart RW Jr and Hall FL: Systemic administration of a matrix-targeted retroviral vector is efficacious for cancer gene therapy in mice. Hum Gene Ther. 12:193–204. 2001.PubMed/NCBI View Article : Google Scholar

16 

Galanis E, Carlson SK, Foster NR, Lowe V, Quevedo F, McWilliams RR, Grothey A, Jatoi A, Alberts SR and Rubin J: Phase I trial of a pathotropic retroviral vector expressing a cytocidal cyclin G1 construct (Rexin-G) in patients with advanced pancreatic cancer. Mol Ther. 16:979–984. 2008.PubMed/NCBI View Article : Google Scholar

17 

Chawla SP, Chua VS, Fernandez L, Quon D, Saralou A, Blackwelder WC, Hall FL and Gordon EM: Phase I/II and phase II studies of targeted gene delivery in vivo: Intravenous Rexin-G for chemotherapy-resistant sarcoma and osteosarcoma. Mol Ther. 17:1651–1657. 2009.PubMed/NCBI View Article : Google Scholar

18 

Chawla SP, Chawla NS, Quon D, Chua-Alcala V, Blackwelder WC, Hall FL and Gordon EM: An advanced phase 1/2 study using an XC-targeted gene therapy vector for chemotherapy resistant sarcoma. Sarcoma Res Int. 3(1024)2016.

19 

Bruckner H, Chawla SP, Liu S, Assudani N, Hall FL and Gordon EM: Phase I-II study using Rexin-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast: A ten-year follow-up. Presented at the 2019 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting. ASGCT, Washington, DC, Abstract 273, 2019.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Morse MA, Chawla SP, Wong TZ, Bruckner HW, Hall FL and Gordon EM: Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review. Mol Clin Oncol 15: 186, 2021.
APA
Morse, M.A., Chawla, S.P., Wong, T.Z., Bruckner, H.W., Hall, F.L., & Gordon, E.M. (2021). Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review. Molecular and Clinical Oncology, 15, 186. https://doi.org/10.3892/mco.2021.2348
MLA
Morse, M. A., Chawla, S. P., Wong, T. Z., Bruckner, H. W., Hall, F. L., Gordon, E. M."Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review". Molecular and Clinical Oncology 15.3 (2021): 186.
Chicago
Morse, M. A., Chawla, S. P., Wong, T. Z., Bruckner, H. W., Hall, F. L., Gordon, E. M."Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review". Molecular and Clinical Oncology 15, no. 3 (2021): 186. https://doi.org/10.3892/mco.2021.2348
Copy and paste a formatted citation
x
Spandidos Publications style
Morse MA, Chawla SP, Wong TZ, Bruckner HW, Hall FL and Gordon EM: Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review. Mol Clin Oncol 15: 186, 2021.
APA
Morse, M.A., Chawla, S.P., Wong, T.Z., Bruckner, H.W., Hall, F.L., & Gordon, E.M. (2021). Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review. Molecular and Clinical Oncology, 15, 186. https://doi.org/10.3892/mco.2021.2348
MLA
Morse, M. A., Chawla, S. P., Wong, T. Z., Bruckner, H. W., Hall, F. L., Gordon, E. M."Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review". Molecular and Clinical Oncology 15.3 (2021): 186.
Chicago
Morse, M. A., Chawla, S. P., Wong, T. Z., Bruckner, H. W., Hall, F. L., Gordon, E. M."Tumor protein p53 mutation in archived tumor samples from a 12‑year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long‑term survival with DeltaRex‑G: A case report and literature review". Molecular and Clinical Oncology 15, no. 3 (2021): 186. https://doi.org/10.3892/mco.2021.2348
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team