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
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
- Published online on: July 8, 2021 https://doi.org/10.3892/mco.2021.2348
- Article Number: 186
Copyright: © Morse et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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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.