Improving adenoviral vectors and strategies for prostate cancer gene therapy

Abstract

Gene therapy has been evaluated for the treatment of prostate cancer and includes the application of adenoviral vectors encoding a suicide gene or oncolytic adenoviruses that may be armed with a functional transgene. In parallel, versions of adenoviral vector expressing the p53 gene (Ad-p53) have been tested as treatments for head and neck squamous cell carcinoma and non-small cell lung cancer. Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach. To achieve better functionality, improvements in the gene transfer system and the therapeutic regimen may be required. We have developed adenoviral vectors whose transgene expression is controlled by a p53-responsive promoter, which creates a positive feedback mechanism when used to drive the expression of p53. Together with improvements that permit efficient transduction, this new approach was more effective than the use of traditional versions of Ad-p53 in killing prostate cancer cell lines and inhibiting tumor progression. Even so, gene therapy is not expected to replace traditional chemotherapy but should complement the standard of care. In fact, chemotherapy has been shown to assist in viral transduction and transgene expression. The cooperation between gene therapy and chemotherapy is expected to effectively kill tumor cells while permitting the use of reduced chemotherapy drug concentrations and, thus, lowering side effects. Therefore, the combination of gene therapy and chemotherapy may prove essential for the success of both approaches.

RETRACTED: Correlation between ER, PR, P53, Ki67 expression, and high-risk HPV infection in patients with different levels of cervical intraepithelial neoplasia

“…ER and PR may participate in abnormal proliferation and inhibit normal cell apoptosis. 23 P53 gene abnormality is closely related to the carcinogenesis of cervical epithelial cells. P53 gene mutation exists in cervical squamous intraepithelial lesions.…”

Correlation between ER, PR, P53, Ki67 Expression and High-Risk HPV Infection in Patients with Different Levels of Cervical Intraepithelial Neoplasia

“…Especially HPV infection is not the only pathogenic factor of cervical squamous intraepithelial lesions. The functional changes of oncogenes and tumor suppressor genes also play a key role in the occurrence and development of cervical squamous intraepithelial of DNA replication and transcription during endometrial cell proliferation, while progesterone has antagonistic effect on estrogen, which can make dysplasia cells mature and down-regulate at the level of transcription and post-transcription [22] . Some studies have shown that ER and PR are most expressed in normal endometrium, but less expressed in cancer.…”

Reduced pim‑1 expression increases chemotherapeutic drug sensitivity in human androgen‑independent prostate cancer cells by inducing apoptosis

“…Gene therapy has brought about a breakthrough for the treatment of prostate cancer, and a number of studies have identified a substantial number of genes that may be potential targets for the treatment of this malignancy (11,12). In the present study, AIPC cell lines PC3 and DU145, which do not respond to androgens, glucocorticoids or epidermal/fibroblast growth factors, were selected as models (13,14).…”