Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 279

Table 6.3 Current Clinical Studies for Cancer Gene Therapy

Primary and Metastatic Liver Cancer Bladder Carcinoma, Malignant Melanoma

Metastatic colon carcinoma Primary and metastatic ovarian cancer

Small cell lung cancer Brain tumors

Lung cancer (NSCLC) Head and neck squamous cell carcinoma

Malignant mesothelioma Persistent multiple myeloma

Prostrate cancer Refractory non-Hodgkin's lymphoma

Renal carcinoma Acute myelogenous leukemia

Refractory neuroblastoma Chronic myelogenous leukemia

Primary and metastatic breast cancer Acute leukemia

Owing to recent advances in early detection and treatments, there has been a steady
decline in prostate cancer-specific mortality since the1990s. Treatment options for
newly diagnosed, clinically localized prostate cancer include surgery, conformal
radiotherapy, and androgen suppression therapy. These treatments are not curative but
instead result in an extension of survival, which can be modest. However, resistance
to these treatment regimens often occurs in advanced or recurrent cancer. Therefore,
there is a need for new therapies for advanced metastatic prostrate cancer [40] .
Prostrate cancer is a suitable candidate for gene therapy due to the following reasons:

l The prostrate is an accessory organ that is easily accessible for delivering the desired genes
in localized diseases rather than administrating by the systemic route; that is, in situ treat-
ments are highly feasible.
l Several tissue-specific antigens like prostate-specific antigen, prostate-specific membrane
antigen, and human osteocalcin, among others, have been overexpressed in the prostrate [41] .
l A large number of prostate-unique promoters are available.
A number of gene therapy strategies are utilized for the treatment of prostrate cancer
gene therapy. Next, we discuss in brief these approaches in preclinical and clinical
settings.

6.3.1.1 Suicide Gene Therapy
Suicide gene therapy, also known as gene-directed enzyme prodrug therapy
(GDEPT), is the most commonly used approach for solid tumors. The suicide genes,
when transduced into target cells, convert inactive prodrugs into cytotoxic metabo-
lites for the host cells. Herpes simplex virus-thymidine kinase (HSV- tk ) with the
ganciclovir (GCV) system has been widely used for prostrate cancer. This system
has been proven to be effective in animal models of human prostrate cancer using
adenoviral vectors [42,43] . HSV- tk with the GCV system has been used in a num-
ber of clinical trials using adenoviral vectors for localized prostrate cancer by an
in situ approach [44-46] . The cytosine deaminase/5-fluorocytosine (CD/5-FC) sys-
tem alone and in combination with Escherichia coli uracil phosphoribosyltransfer-
ase (UPRT) has been used with adenoviral vectors for prostrate cancer [47] . The