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Page 130 Bibi et al. J Transl Genet Genom 2024;8:119-161 https://dx.doi.org/10.20517/jtgg.2023.50

accessing the telomeres and suppress its activity. G-quadruplex stabilizers include BRACO-19, RHPS4,
TMPyP4, etc. [185,187] . Epigenetic modulators are medications that change the methylation or acetylation of the
hTERT gene promoter region to modify the chromatin structure and gene expression. Trichostatin A
(TSA), 5-aza-2'-deoxycytidine (DAC), and valproic acid (VPA) are a few examples of epigenetic
modulators . Signaling system inhibitors are drugs that target upstream or downstream signaling
[187]
pathways, such as PI3K/AKT/mTOR, catenin /- Wnt, NF-B, and MAPK, which regulate hTERT expression
or activity .
[187]

Therefore, further investigation and improvement are required to enhance the formulation and
administration of hTERT immunotherapy for prostate cancer. Additionally, combination therapies that
target various biological components of hTERT and synergize with other treatment modalities, such as
chemotherapy, radiation, or hormone therapy, may improve the prognosis for prostate cancer patients.

Survivin
Survivin, an inhibitor of apoptosis and activator of proliferation, is produced by numerous tissues during
fetal development, but its expression becomes essentially nonexistent in differentiated cells . However, in
[113]
many human malignancies, including PCa, survivin is significantly overexpressed and its presence is
correlated with tumor development, poorer prognosis for malignant illness, and medication resistance.
Survivin has been identified as a modulator of antiandrogen treatment resistance in PCa [111,188,189] . Various
preclinical models have shown that immunotherapeutic approaches targeting survivin can elicit T cell
responses and antitumor activity [190,191] . Survivin is, therefore, a possible target for cancer treatment,
particularly in immunotherapy, which aims to activate the immune system to identify and eliminate cancer
cells [192,193] .

Given its crucial role in tumor survival and resistance, survivin becomes a particularly pertinent
immunotherapeutic target in prostate cancer. Targeting survivin, along with other tumor antigens in
prostate cancer, necessitates the use of various immunotherapeutic strategies that have either been
established or are currently under research. Although several of these methods have demonstrated
encouraging results in clinical trials, they are not without difficulties and restrictions. Thus, further research
is required to maximize the effectiveness and safety of various therapies and to determine the ideal patients
for each form of treatment.

HER-2/neu, EGFR, HER-4 (Epidermal Growth Factor Family)
The ErbB receptor tyrosine kinase family, which includes cell surface proteins such as EGFR, HER 1, HER
2/neu, and HER 4, is often found to be overexpressed in various types of tumors, including PCa . These
[110]
proteins present promising targets for T cells or antibody-dependent immunotherapy. Specifically,
overexpression of HER 2/neu in early PCa is linked to adverse clinical results, including primary recurrence
and reduced overall survival [194,195] . HER 2/neu is included in the development of prostate cancer towards
androgen independence. A wide array of HER 2/neu-derived proteins that are HLA class I-, class II-
restricted have been identified . Furthermore, mice models of various types of solid tumors have
[196]
demonstrated the efficacy of active immunotherapy . In preclinical models, treatments involving
[197]
monoclonal anti-HER 2/neu antibodies have been investigated. In both androgen-dependent xenograft
models and a combined therapy approach including HRPC xenograft models with tyrosine kinase
inhibitors, administration of trastuzumab significantly inhibited the growth of established tumors [197,198] .
Additionally, in a SCID mouse model, specifically engineered T lymphocytes targeting Her-2/neu
successfully attacked prostate cancer (bone marrow metastases) .
[199]