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Updated: Jan 27, 2026
Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis
Published on: May 12, 2019
Combination of cabazitaxel and p53 gene therapy abolishes prostate carcinoma tumor growth
Rodrigo Esaki Tamura1,2, Marlous G Lana1, Eugenia Costanzi-Strauss3
1Viral Vector Laboratory, Center for Translational Investigation in Oncology/LIM24, Cancer Institute of São Paulo, School of Medicine, University of São Paulo, SP, Brazil.
Abstract:
For patients with metastatic prostate cancer, the 5-year survival rate of 31% points to a need for novel therapies and improvement of existing modalities. We propose that p53 gene therapy and chemotherapy, when combined, will provide superior tumor cell killing for the treatment of prostate carcinoma. To this end, we have developed the AdRGD-PGp53 vector which offers autoregulated expression of p53, resulting in enhanced tumor cell killing in vitro and in vivo. Here, we combined AdRGD-PGp53 along with the chemotherapy drugs used in the clinical treatment of prostate carcinoma, mitoxantrone, docetaxel, or cabazitaxel. Our results indicate that all drugs increase phosphorylation of p53, leading to improved induction of p53 targets. In vitro experiments reveal that AdRGD-PGp53 sensitizes prostate cancer cells to each of the drugs tested, conferring increased levels of cell death. In a xenograft mouse model of in situ gene therapy, AdRGD-PGp53 treatment, when combined with cabazitaxel, drastically reduced tumor progression and increased survival rates to 100%. Strikingly, we used a sub-therapeutic dose of cabazitaxel thus avoiding leukopenia, yet still showed potent anti-tumor effects when combined with AdRGD-PGp53 in this mouse model. The AdRGD-PGp53 approach warrants further development for its application in gene therapy of prostate carcinoma.
Insights
Combining p53 gene therapy with chemotherapy offers a promising new treatment for prostate cancer. This novel approach significantly enhanced tumor cell killing and improved survival rates in preclinical models.
Area of Science:
- Oncology
- Gene Therapy
- Cancer Research
Background:
- Metastatic prostate cancer has a poor 5-year survival rate (31%), necessitating innovative therapeutic strategies.
- Current treatments for prostate cancer require improvement to enhance efficacy and reduce side effects.
Purpose of the Study:
- To evaluate the combined efficacy of p53 gene therapy (AdRGD-PGp53) and chemotherapy in treating prostate cancer.
- To determine if AdRGD-PGp53 sensitizes prostate cancer cells to standard chemotherapeutic agents.
Main Methods:
- Developed AdRGD-PGp53 vector for autoregulated p53 expression.
- Combined AdRGD-PGp53 with mitoxantrone, docetaxel, or cabazitaxel in vitro and in vivo.
- Utilized a xenograft mouse model for in situ gene therapy and chemotherapy assessment.
Main Results:
- AdRGD-PGp53 enhanced p53 target induction when combined with chemotherapy drugs.
- Prostate cancer cells were sensitized to chemotherapy by AdRGD-PGp53, leading to increased cell death.
- Combination therapy with AdRGD-PGp53 and a sub-therapeutic dose of cabazitaxel resulted in 100% survival in a mouse model, avoiding leukopenia.
Conclusions:
- The AdRGD-PGp53 vector shows significant potential for enhancing prostate cancer treatment.
- Combining p53 gene therapy with chemotherapy, particularly cabazitaxel, offers a potent anti-tumor effect with reduced toxicity.
- Further development of AdRGD-PGp53 is warranted for clinical application in prostate carcinoma gene therapy.
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