About this Research Topic
Prostate cancer (PC) is the most common cancer among men in the United States and worldwide. Approximately one in nine men will be diagnosed with prostate cancer during their lifetime. In 2022, there will be an estimated 268,490 new prostate cancer cases in the United States, resulting in nearly 34,500 deaths. Commonly, prostate cancer patients with recurrent disease undergo androgen-deprivation therapy (ADT) after local therapy. However, resistance invariably occurs, and in these cases, cancer has become "castration-resistant prostate cancer" (CRPC). It may spread beyond the prostate, developing into lethal metastatic castration-resistant prostate cancer (mCRPC).
The normal structure of DNA is essential for healthy cell growth, but DNA becomes damaged or mutated. DNA damage repair (DDR) genes help maintain DNA integrity. Recent deep sequencing of mCRPC patients has revealed a surprisingly high frequency of aberrations in several DNA damage repair (DDR) pathway genes. Aberrations, both somatic and germline, of BRCA2, a hallmark DDR gene, were seen in 13.3% of men with mCRPC; germline mutations were present in 5.3%. Prostate cancer patients harboring tumors with DDR defects have been found to have more aggressive high-grade carcinoma, advanced metastatic disease, resistance to ADT, and poorer survival. There is a lack of understanding of the functional impact and biological significance of the alteration/deficiencies of DDR pathways in driving prostate cancer progression, therapy resistance, and metastasis.
Given these observations highlighting the crucial importance of DDR alterations in prostate cancer progression, in this Research Topic, we aim to comprehensively analyze and highlight the various aspects of DDR alterations in the development of lethal prostate cancer. This Research Topic's central premise is to understand the molecular insights associated with DDR alterations and the biology of aggressive and metastatic prostate cancer to improve outcomes for men with this lethal disease in the future.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
The normal structure of DNA is essential for healthy cell growth, but DNA becomes damaged or mutated. DNA damage repair (DDR) genes help maintain DNA integrity. Recent deep sequencing of mCRPC patients has revealed a surprisingly high frequency of aberrations in several DNA damage repair (DDR) pathway genes. Aberrations, both somatic and germline, of BRCA2, a hallmark DDR gene, were seen in 13.3% of men with mCRPC; germline mutations were present in 5.3%. Prostate cancer patients harboring tumors with DDR defects have been found to have more aggressive high-grade carcinoma, advanced metastatic disease, resistance to ADT, and poorer survival. There is a lack of understanding of the functional impact and biological significance of the alteration/deficiencies of DDR pathways in driving prostate cancer progression, therapy resistance, and metastasis.
Given these observations highlighting the crucial importance of DDR alterations in prostate cancer progression, in this Research Topic, we aim to comprehensively analyze and highlight the various aspects of DDR alterations in the development of lethal prostate cancer. This Research Topic's central premise is to understand the molecular insights associated with DDR alterations and the biology of aggressive and metastatic prostate cancer to improve outcomes for men with this lethal disease in the future.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Keywords: prostate cancer, dna damage repair, cancer progression, metastasis
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
