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Page 144 Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50

transfection capacity, and significantly lower levels of transgenic expression. Overall, every type of vector,
viral and nonviral, has specific benefits and drawbacks. Nevertheless, they can be modified chemically and
physically by attaching targeting compounds, additional proteins, and peptides in the form of promoters to
enhance gene transport [298-301] .

Potent viral gene therapies in prostate cancer
In gene therapy, viral vectors are utilized to deliver genetic materials. Gene therapy approaches that have
been developed [Figure 5] and are under investigation for prostate cancer include:

Suicide gene therapy
In this method, a gene encoding an enzyme that can change a prodrug from harmless to toxic is delivered
by a viral vector. When the prodrug is given systemically, it kills tumor cells that produce the enzyme
specifically, leaving healthy cells unharmed. Thymidine kinase (HSV-tk), for instance, is an enzyme that
may phosphorylate ganciclovir, a nucleoside analog that stops DNA synthesis and causes apoptosis in
herpes simplex virus infection. Patients with prostate cancer localized to a particular locality, who
participated in a clinical experiment wherein HSV-tk was delivered into the prostate gland via an
adenovirus vector, experienced a noteworthy decrease in both tumor volume and PSA levels [269,302] .

Tumor suppressor gene therapy
This method delivers a gene that encodes a tumor suppressor protein, a protein that can control apoptosis,
the cell cycle, or DNA repair, using a viral vector. When endogenous tumor suppressor genes are deleted or
altered in tumor cells, the tumor suppressor protein can either induce cell death or restore normal cell
function. A tumor suppressor protein called REIC/Dkk-3 has the ability to block Wnt signaling and trigger
endoplasmic reticulum stress-mediated apoptosis. In a clinical experiment, patients suffering from
castration-resistant prostate cancer experienced notable reductions in tumor volume and PSA levels
[303]
following the delivery of REIC/Dkk-3 to their prostate glands using an adenovirus vector .
Cytokine gene therapy
This method delivers a gene that codes for a cytokine, a protein that can influence the immune system and
have antitumor properties, via a viral vector. The cytokine can suppress tumor development and
angiogenesis, improve antigen presentation, and activate immune cells both locally and systemically. In a rat
model of prostate cancer, employing an adenovirus vector to deliver the cytokine interleukin-12 to TAMs
could cause their reprogramming from an M2-like to an M1-like phenotype and prevent tumor growth and
[304]
metastasis .
Viral vector-gene therapy offers the potential for straightforward tumor destruction without the
requirement for long-lasting transgene expression, serving as a targeted approach for various types of
prostate cancer. Apart from intratumoral delivery, experiments have been conducted on tumor targeting
using vectors particularly engineered for that purpose, which involves using tumor-specific promoters and
utilizing oncolytic viruses .
[288]

Corrective gene therapy
One kind of gene treatment called "corrective gene therapy" tries to fix the genetic flaws or mutations that
either cause or aggravate prostate cancer. It operates under the premise that cancer cells can be stopped
from proliferating and spreading by injecting a functional or normal copy of a gene into them . Viral or
[294]
nonviral transport vehicles are used to transfer the genes to the target cells in corrective gene therapy.