a more recent investigation conducted by Zhang and colleagues, mice were admin­istered an oral dosage of a minicircle plasmid containing the SOD2 gene. Subsequently, these animals were subjected to irradiation of 31Gy specically tar­geting the esophagus. The survival rates of the mice that were administered the SOD2 plasmid were shown to be superior when compared to the control group. In a similar vein, it was shown that mice administered the plasmid intravenously had enhanced rates of survival when subjected to whole-body irradiation of 9.75Gy [58]. In a research conducted by Josson’s team, it was shown that PC-3 cells, which are indicative of high-grade prostate cancer, exhibited greater resistance to radiation and had higher nucleus levels of RelB compared to LNCaP cells, which are repre­sentative of low-grade prostate cancer [55]. According to the research conducted by Josson etal., it was shown that the levels of SOD2 were up in both PC-3 and LNCaP cells after exposure to radiation. However, the LNCaP cells exhibited a higher pres­ence of superoxide radicals compared to the PC-3 cells. The introduction of an exogenous SOD2 mimic resulted in an increased radioresistance of the LNCaP cells. The PC-3 cell population exhibited higher baseline levels of SOD2 and greater activity of SOD2 compared to the LNCaP cells. A comprehensive depiction emerges when the ndings of this investigation are juxtaposed with the ndings of the afore­mentioned study by Venkataraman’s team, which demonstrated that PC-3 cells exhibited diminished levels of SOD2in comparison to immortalized prostate epi­thelial cells. Collectively, recent investigations align with the concept that the level of SOD2 diminishes upon cancer initiation and escalates during the advancement of the ailment [59].

Following the failure of initial ADT, using bicalutamide or luteinizing hormone­releasing hormone (LHRH) antagonists, patients may receive hormone-based treat­ments like abiraterone which can modify the production of androgens within the tumor itself [67]. This alteration is particularly relevant in cases of CRPC.Additionally, medications such as enzalutamide and apalutamide can effec­tively suppress any remaining androgen responses in individuals with CRPC [68,

69]. Following the near-inevitable lack of success shown in the later androgen-

based therapies [70], there is a shift toward using less targeted, replication-based chemotherapies that are more hazardous, such as taxane treatments, for the manage­ment of CRPC.There is a potential for the development of other targeted chemo­therapies, including olaparib, that specically address the subset of prostate tumors characterized by DNA damage repair deciencies. Recent clinical studies have shown encouraging results in this regard [71]. Currently, the oncologist’s options for intervention are limited to palliative measures in order to alleviate the progres­sion of the most lethal manifestation of the illness, characterized by a weakly dif­ferentiated histology often associated with higher Gleason grades. The lesions of advanced CRPC have either a basaloid or neuroendocrine character, known as neu­roendocrine prostate cancer (NEPC), and eventually have an unfavorable progno­sis [72].

The use of combination therapy, which includes the administration of both tax­anes and androgen signaling suppression, has shown improved survival outcomes in patients who have just been diagnosed with high-grade metastatic illness [73]. Nevertheless, it is worth noting that several alternative immunotherapies have not shown comparable potential in the treatment of prostate cancer so far, as their effec­tiveness has been limited to a small subset of patients [74]. This is in contrast to the signicant improvements reported in small-cell lung cancer, melanoma, and certain types of leukemias [75]. However, ADT continues to be the predominant approach for the rst pharmacological intervention in prostate cancer clinical care. Prostate cancer patients who undergo hormone treatment often see improvements for a dura­tion of 1–4years, with a few exceptions where remission may last for as long as 10 years. The future prospects of androgen deprivation therapy seem to be closely tied to the development of novel and enhanced androgen signaling inhibitors [76]. This trajectory, however, necessitates substantial nancial investments from the pharma­ceutical sector and imposes additional burdens on healthcare systems. Clinical stud­ies have examined the efcacy of combination therapies and other forms of complete androgen blocking, including both continuous and intermittent approaches [77]. Nevertheless, the recurrence of cancer persists despite the seemingly improved sur­vival rates seen in groups receiving intermittent treatment [78], suggesting that this therapeutic approach is likely not being fully used. The lack of a denitive explana­tion for the limited efcacy of a combination of androgen signaling inhibitors in achieving remission or cure in CRPC, despite the tumor cells’ apparent need for androgens, remains unclear [79].