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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 129

[176]
[174]
adjuvant CpG 79093 , which boosts immune responses, or using the viral vector MVA-NY-ESO-1 ,
which transmits the desired gene. All these studies have shown that the NY-ESO-1 vaccine can stimulate or
elicit NY-ESO-1-specific immune responses in prostate cancer subjects, which may have certain therapeutic
advantages, such as tumor regression or disease stabilization [173,176] . However, to establish the long-term
results and ideal practices of NY-ESO-1 immunotherapy for prostate cancer, more research is required.

Overexpressed proteins in prostate cancer, including tumors
Many proteins, including those associated with prostate cancer, exhibit overexpression across various
cancers. Overexpression occurs when cells produce an excess amount of a specific protein beyond what is
required. This phenomenon can significantly influence the growth, survival, and functionality of cells.
Several of the proteins that are overexpressed in prostate cancer include [Figure 2]:

Parathyroid hormone-related protein
PTHrP plays a crucial role in bone development by binding to receptors on osteoblasts. Its involvement in
the formation of bone metastases is particularly pronounced in PCa and other epithelial-origin
malignancies [177,178] . Numerous prostate cancer cell lines and metastatic bone lesions exhibit the presence of
PTHrP. Through activation of several pathways and interaction with other molecules, PTHrP can promote
tumor growth, survival, invasion, and metastasis. Additionally, PTHrP can confer resistance to apoptosis in
prostate cancer cells, which is triggered by various stimuli, including chemotherapy or radiation. By
stimulating angiogenesis and osteolysis (breakdown of bones), PTHrP has an impact on the TME (tumor
microenvironment) [179,180] .

The role of PTHrP in prostate cancer is complex and not fully understood. However, it is obviously
implicated in many facets of prostate cancer initiation and progression. As a result, PTHrP may serve as a
potent biological marker for assessing the potential malignancy of prostate cancer, as well as a promising
target for therapy aimed at retarding tumor growth and improving patient survival.

Human telomerase reverse transcriptase
In the majority of human malignancies, there is an overexpression of human telomerase reverse
transcriptase (hTERT) is overexpressed, making it a crucial target for cancer therapeutics. Most non-
transformed somatic cells lack this molecule, although it is present in over 85% of human malignancies,
[181]
including PCa . Research has identified a number of naturally occurring restricted epitopes to HLA-
A*0201 of CTL that effectively generate peptide-specific and tumor-lysing CTLs in both In vitro and in vivo
settings [111,182] .

Additionally, in the initial instances of hTERT-based immunization experiments, direct evidence emerged
linking the formation of tumor-infiltrating T cells to positive clinical outcomes. A number of clinical trials
were initiated and are ongoing to evaluate the ability of hTERT to treat prostate cancer [183,184] .

Dendritic cells (DCs), specialized antigen-presenting cells, are used in cell-based vaccination to introduce
hTERT antigens to the immune system. To effectively induce anti-hTERT immunity, DCs can be loaded
with hTERT peptides, mRNA, or DNA, and then administered to patients. This tactic has also been put to
the test in prostate cancer clinical trials [183,184] . TERT inhibitors are tiny compounds that bind specifically to
the hTERT catalytic site, thereby inhibiting its function, shortening telomeres and inducing apoptosis or
cellular senescence. Examples of TERT inhibitors include substances like BIBR1532, MST-312, and
GRN163L [185,186] . G-quadruplex stabilizers are substances that bind to the G-rich sequences in telomeric
DNA, leading to the formation of G-quadruplexes, four-stranded structures that block hTERT from