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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.

dc.contributor.author Morse, Michael A
dc.contributor.author Chawla, Sant P
dc.contributor.author Wong, Terence Z
dc.contributor.author Bruckner, Howard W
dc.contributor.author Hall, Frederick L
dc.contributor.author Gordon, Erlinda M
dc.date.accessioned 2022-01-01T14:57:22Z
dc.date.available 2022-01-01T14:57:22Z
dc.date.issued 2021-09
dc.identifier MCO-0-0-02348
dc.identifier.issn 2049-9450
dc.identifier.issn 2049-9469
dc.identifier.uri https://hdl.handle.net/10161/24158
dc.description.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 (<i>CCNG1</i>) oncogene. DeltaRex-G inhibits the <i>CCNG1</i> function of promoting cell competence and survival through the commanding <i>CCNG1</i>/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, 3x10<sup>11</sup> 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) (<i>G199V</i>) 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 <i>CCNG1</i>/CDK/Myc/Mdm2/p53 axis, which regulates proliferative cell competence, DNA fidelity and survival<i>.</i> 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.
dc.language eng
dc.publisher Spandidos Publications
dc.relation.ispartof Molecular and clinical oncology
dc.relation.isversionof 10.3892/mco.2021.2348
dc.subject CCNG1 inhibitor
dc.subject TP53
dc.subject cancer gene therapy
dc.subject case report
dc.subject pancreatic adenocarcinoma
dc.title 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.
dc.type Journal article
duke.contributor.id Wong, Terence Z|0019072
dc.date.updated 2022-01-01T14:57:19Z
pubs.begin-page 186
pubs.issue 3
pubs.organisational-group School of Medicine
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Radiology, Nuclear Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Duke
pubs.organisational-group Institutes and Centers
pubs.organisational-group Radiology
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Medicine
pubs.publication-status Published
pubs.volume 15
duke.contributor.orcid Wong, Terence Z|0000-0002-3830-1779


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