Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy
| Autor: | Eric Hastie, Valery Z. Grdzelishvili, Christian Bressy |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
p53
0301 basic medicine Cancer Research tumor suppressor Genetic enhancement Transgene p73 cancer gene therapy Review Vectors in gene therapy Biology lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine medicine tumor protein p53 Pharmacology (medical) TP53 Virotherapy oncolytic virus p63 Cancer lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 3. Good health Oncolytic virus Clinical trial 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell combination treatment Cancer research Molecular Medicine virotherapy |
| Zdroj: | Molecular Therapy: Oncolytics, Vol 5, Iss C, Pp 20-40 (2017) Molecular Therapy Oncolytics |
| ISSN: | 2372-7705 |
| Popis: | Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy. |
| Databáze: | OpenAIRE |
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