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Ref Type | Journal Article | ||||||||||||
PMID | (15608394) | ||||||||||||
Authors | Baek JH, Agarwal ML, Tubbs RR, Vladisavljevic A, Tomita H, Bukowski RM, Milsom JW, Kim JM, Kwak JY | ||||||||||||
Title | In vivo recombinant adenovirus-mediated p53 gene therapy in a syngeneic rat model for colorectal cancer. | ||||||||||||
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Abstract Text | The p53 gene has a significant role in controlling genomic stability of cancer. The purpose of this study was to evaluate the tumor response of allograft colorectal tumor treated with Ad5CMV-p53 in a syngeneic rat model. Two weeks after the inoculation of WB-2054-M5 tumor cells in the flank of rats, rats were randomly assigned by tumor size to one of three groups (n=18 in each): phosphate buffered saline (PBS), Ad5CMV, and Ad5CMV-p53. Recombinant adenovirus or PBS was administered through intratumoral injection at three divided doses every other day for 4 weeks. Apoptosis of the tumors was evaluated using TUNEL assay. After 2 and 4 weeks of treatment, the volume (cm(3)) of tumors in PBS, Ad5CMV, and Ad5CMV-p53 was as follows: 2 week: 1.66 +/-0.43, 1.40 +/-0.47, 0.75 +/-0.26 (p<0.001), 4 week: 4.41 +/-0.88, 3.93 +/-1.86, 2.33 +/-0.51 (p<0.001). Tumor growth showed no statistically significant difference between the PBS and Ad5CMV groups (6-week vol. p=0.32). The TUNEL assay results revealed more apparent apoptotic cells in Ad5CMV-p53-treated tumors than in other groups. Growth of allograft colorectal cancer in the syngeneic rat model was significantly suppressed by intratumoral Ad5CMV-p53 gene therapy. These results demonstrate that gene replacement therapy with p53 may provide a novel modality of treatment in conjunction with other present treatments for metastatic colorectal cancer. |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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TP53 loss | colorectal cancer | predicted - sensitive | Ad5CMV-p53 gene | Preclinical | Actionable | In a preclinical study, Ad5CMV-p53 gene therapy suppressed growth of allograft colorectal cancer in rat models (PMID: 15608394). | 15608394 |