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Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50 Page 145

Using adenovirus vectors to transmit the p53 gene - a tumor suppressor gene frequently altered or
destroyed in prostate cancer - is one instance of corrective gene therapy for the disease [294,303] .

Senescence, apoptosis, or cell cycle arrest can all be brought on by the p53 gene in reaction to stress signals
or DNA damage. Corrective gene therapy can cause prostate cancer cells to self-destruct and stop growing
by restoring the expression of p53 in such cells.

The delivery of the PTEN gene, another tumor suppressor gene frequently lost or deactivated in prostate
cancer, using adeno-associated virus (AAV) vectors is another example of corrective gene therapy for the
disease. Through antagonistic action on the PI3K/AKT signaling pathway, frequently hyperactivated in
prostate cancer, the PTEN gene can control cell proliferation, survival, and invasion. Corrective gene
therapy can lessen the multiplication and invasiveness of prostate cancer cells by restoring the response of
PTEN in those cells [294,305] .

Prostate cancer corrective gene therapy is currently in the experimental stage and has not yet received
clinical approval. There are ongoing or completed clinical trials calculating the effectiveness and safety of
this methodology. For instance, in a trial of gene-directed enzyme prodrug therapy (GDEPT) for early
prostate cancer, a gene that can activate the innocuous medication CB1954 into a potent anti-cancer drug
was delivered by a specially treated virus. Additionally, for locally advanced prostate cancer, the conjunction
[305]
of adenovirus-mediated p53 gene therapy with radiation therapy was investigated in different trials .
Although these trials have yielded some encouraging findings, further investigation is required to address
the obstacles and restrictions associated with corrective gene therapy, including limited transfection
efficiency, immunological response, specificity, and toxicity [294,305] .

Potent nonviral gene therapies in prostate cancer
Since multiple genes in malignant cells are impacted by different genetic abnormalities, cancer is thought to
be a genetic condition. Tumor suppressor genes such as TP53 and NM23, and oncogenes such as RAS,
c-MYC, BCL2, and c-MET are the most commonly affected. Tumor suppressor genes play a crucial role
in regulating normal cell death and the elimination of cellular waste products. Deactivation of these
genes, through mutation or absence, can promote cell malignancy. Oncogenes, on the other hand, are
responsible for maintaining steady cell proliferation and their activation can promote cancer cell
[293]
growth . Although genome editing medicines have traditionally been delivered using viral vectors in
lab settings and clinical trials, their translation has been severely hampered by the possible immunogenic
risks associated with viral carriers. However, nonviral administration methods have emerged as a
promising alternative. Nonviral delivery systems, intentionally synthesized and with fewer safety
concerns, offer a viable option. Although they have somewhat lower delivery efficiency compared to
viral delivery systems, they present a safer alternative with reduced immunogenic risks.

Numerous genes are implicated in genetic alterations in prostate cancer. For example, it was discovered that
approximately fifty and thirty-five percent of advanced-stage prostate cancer cases exhibit mutations in the
tumor suppressor gene TP53 and retinoblastoma, respectively .
[293]
Mutations in genes cause uncontrollable cell development. TP53 primarily plays a role in maintaining the
cell life cycle and repairing DNA damage. Additionally, it has been discovered that certain cases of prostate
cancer had disruptions in the GSTP1 gene. GSTP1's primary physiological function is carcinogen
[293]
detoxification, and its deactivation promotes carcinogenesis . According to applications, potent nonviral
gene therapies include: