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利用DNA损伤反应进行前列腺癌治疗。

Exploiting the DNA Damage Response for Prostate Cancer Therapy.

作者信息

Stracker Travis H, Osagie Oloruntoba I, Escorcia Freddy E, Citrin Deborah E

机构信息

Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Cancers (Basel). 2023 Dec 23;16(1):83. doi: 10.3390/cancers16010083.

Abstract

Prostate cancers that progress despite androgen deprivation develop into castration-resistant prostate cancer, a fatal disease with few treatment options. In this review, we discuss the current understanding of prostate cancer subtypes and alterations in the DNA damage response (DDR) that can predispose to the development of prostate cancer and affect its progression. We identify barriers to conventional treatments, such as radiotherapy, and discuss the development of new therapies, many of which target the DDR or take advantage of recurring genetic alterations in the DDR. We place this in the context of advances in understanding the genetic variation and immune landscape of CRPC that could help guide their use in future treatment strategies. Finally, we discuss several new and emerging agents that may advance the treatment of lethal disease, highlighting selected clinical trials.

摘要

尽管进行了雄激素剥夺治疗仍进展的前列腺癌会发展为去势抵抗性前列腺癌,这是一种致命疾病,治疗选择很少。在本综述中,我们讨论了目前对前列腺癌亚型以及DNA损伤反应(DDR)改变的理解,这些改变可能易患前列腺癌并影响其进展。我们确定了传统治疗(如放疗)的障碍,并讨论了新疗法的发展,其中许多疗法靶向DDR或利用DDR中反复出现的基因改变。我们将其置于对去势抵抗性前列腺癌(CRPC)的遗传变异和免疫格局理解的进展背景下,这可能有助于指导它们在未来治疗策略中的应用。最后,我们讨论了几种可能推进致命疾病治疗的新型和新兴药物,并重点介绍了选定的临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de05/10777950/8493b14dda99/cancers-16-00083-g001.jpg

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