Progress in gene therapy treatments for prostate cancer

Abstract

Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor‐suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti‐oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.

Adding recombinant AAVs to the cancer therapeutics mix

“…Similar to early research with HCC, many of the gene therapy studies regarding these tumor types have centered on driving expression of suicide genes by promoters like GRP78 and PSA for PCa, and ErbB2 and MUC1 for BCa. 10 , 11 , 56 , 61 , 113 An AAV9 construct using either the non-specific chicken beta actin promoter or the neuron-specific enolase promoter driving expression of soluble TRAIL demonstrated a retardation of a PDX orthotopic glioblastoma tumor model. 122 The breadth of cancers that are being successfully targeting in translational studies, especially those used in PDX models, suggests an exciting and hopeful future in cancer research.…”

“…Regardless of tumor type, once metastasis occurs and the primary tumor spreads to distant secondary sites, the 5-year survival rate of the patient dramatically decreases, emphasizing the need for early effective treatments and metastasis-specific therapies that prolong survival. 1 , 4 , 10 , 22 , 130 , 131 , 132 , 133 , 134 , 135 The cells of a tumor that metastasize to a secondary organ express a genetic profile that is different from the primary tumor, a characteristic of tumor heterogeneity that in some ways makes metastatic cancer its own distinct disease. 130 , 132 , 134 , 136 For example, several groups report specific secretome and genetic profiles of metastatic clones of cancer cell lines compared with the parental line, a biological trait that can be exploited by the engineering versatility of AAVs to specifically and effectively target subgroups of cancers located in either a primary or secondary site.…”

“…Gene therapy treatments designed to target mutated DNA sequences and correct them to restore proper function are being explored and are having a positive impact on multiple disease outcomes, including cancer. 5 , 6 , 7 , 8 , 9 , 10 , 11 In this review, we provide a brief overview of the cancer therapeutics landscape before focusing on the various types of gene therapy yielding encouraging results in preclinical and clinical settings for cancer, including advantages and limitations of these therapies. Finally, we concentrate on the biology and application of adeno-associated viruses (AAVs), one type of viral gene therapy with the potential to make a major impact on the cancer field due to their versatility, low immunogenicity, and long-lasting effects.…”

Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer

“…Androgen receptors have an important role in the development of PCa, and their activation can stimulate proliferation while inhibiting the apoptosis of PCa cells. Therefore, androgen deprivation therapy is the standard first-line treatment for advanced prostate cancer 1 . Castration-resistant prostate cancer (CRPC) is cancer that continues to grow even when the testosterone levels are at or below the castrate level 2 .…”