DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology
Prostate cancer (PCa) has a distinct molecular signature, including characteristic chromosomal translocations, gene deletions and defective DNA damage repair mechanisms. One crucial pathway involved is homologous recombination deficiency (HRD) and it is found in almost 20% of metastatic castrate-resistant PCa (mCRPC). Inherited/germline mutations are associated with a hereditary predisposition to early PCa development and aggressive behavior. BRCA2, ATM and CHECK2 are the most frequently HRD-mutated genes. BRCA2-mutated tumors have unfavorable clinical and pathological characteristics, such as intraductal carcinoma. PARP inhibitors, due to the induction of synthetic lethality, have been therapeutically approved for mCRPC with HRD alterations. Mutations are detected in metastatic tissue, while a liquid biopsy is utilized during follow-up, recognizing acquired resistance mechanisms. The mismatch repair (MMR) pathway is another DNA repair mechanism implicated in carcinogenesis, although only 5% of metastatic PCa is affected. It is associated with aggressive disease. PD-1 inhibitors have been used in MMR-deficient tumors; thus, the MMR status should be tested in all metastatic PCa cases. A surrogate marker of defective DNA repair mechanisms is the tumor mutational burden. PDL-1 expression and intratumoral lymphocytes have ambivalent predictive value. Few experimental molecules have been so far proposed as potential biomarkers. Future research may further elucidate the role of DNA damage pathways in PCa, revealing new therapeutic targets and predictive biomarkers.
机构:
Taipei City Hosp, Renai Branch, Taipei 10629, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Teng, Pai-Chi
Huang, Shu-Pin
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Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol, Kaohsiung 80708, Taiwan
Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Urol, Kaohsiung 80708, Taiwan
Kaohsiung Med Univ, Grad Inst Clin Med, Coll Med, Kaohsiung 80708, Taiwan
Kaohsiung Med Univ, Coll Med, PhD Program Environm & Occupat Med, Kaohsiung 80708, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Huang, Shu-Pin
Liu, Chia-Hsin
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China Med Univ, Res Ctr Canc Biol, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Liu, Chia-Hsin
Lin, Ting-Yi
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Taipei Vet Gen Hosp, Dept Med Res, Taipei 11217, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Lin, Ting-Yi
Cho, Yi-Chun
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China Med Univ, Res Ctr Canc Biol, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Cho, Yi-Chun
Lai, Yo-Liang
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China Med Univ, Grad Inst Biomed Sci, Taichung 40403, Taiwan
China Med Univ Hosp, Dept Radiat Oncol, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Lai, Yo-Liang
Wang, Shu-Chi
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Kaohsiung Med Univ, Dept Med Lab Sci & Biotechnol, Kaohsiung 80708, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Wang, Shu-Chi
Yeh, Hsin-Chih
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Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol, Kaohsiung 80708, Taiwan
Kaohsiung Municipal Tatung Hosp, Dept Urol, Kaohsiung 80145, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Yeh, Hsin-Chih
Chuu, Chih-Pin
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Natl Hlth Res Inst, Inst Cellular & Syst Med, Miaoli 35053, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
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China Med Univ, Res Ctr Canc Biol, Taichung 40403, Taiwan
China Med Univ, Grad Inst Biomed Sci, Taichung 40403, Taiwan
China Med Univ, PhD Program Canc Biol & Drug Discovery, Taichung 40403, Taiwan
Acad Sinica, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Cheng, Wei-Chung
Li, Chia-Yang
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Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung 80708, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
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Niigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, Japan
Niigata Univ, Grad Sch Med & Dent Sci, Dept Signal Transduct Res, Div Mol Oncol, Niigata, JapanNiigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, Japan
Hara, Noboru
Nishiyama, Tsutomu
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Niigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, JapanNiigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, Japan
机构:
St Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
Filippi, Luca
Palumbo, Barbara
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Univ Perugia, Dept Med & Surg, Sect Nucl Med & Hlth Phys, Piazza Lucio Severi 1, I-06132 Perugia, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
Palumbo, Barbara
Bagni, Oreste
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St Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
Bagni, Oreste
Frantellizzi, Viviana
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Sapienza Univ Rome, Dept Radiol Sci Oncol & Anatomo Pathol, I-00185 Rome, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
机构:
Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, England
Univ Cambridge, Canc Res UK Cambridge Inst, Canc Res UK Cambridge Ctr, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England
Pinilla, Karen
Drewett, Lynsey M.
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Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England
Drewett, Lynsey M.
Lucey, Rebecca
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Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England
Lucey, Rebecca
Abraham, Jean E.
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Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, England
Univ Cambridge, Canc Res UK Cambridge Inst, Canc Res UK Cambridge Ctr, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England
机构:
Taipei City Hosp, Renai Branch, Taipei 10629, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Teng, Pai-Chi
Huang, Shu-Pin
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol, Kaohsiung 80708, Taiwan
Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Urol, Kaohsiung 80708, Taiwan
Kaohsiung Med Univ, Grad Inst Clin Med, Coll Med, Kaohsiung 80708, Taiwan
Kaohsiung Med Univ, Coll Med, PhD Program Environm & Occupat Med, Kaohsiung 80708, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Huang, Shu-Pin
Liu, Chia-Hsin
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h-index: 0
机构:
China Med Univ, Res Ctr Canc Biol, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Liu, Chia-Hsin
Lin, Ting-Yi
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h-index: 0
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Taipei Vet Gen Hosp, Dept Med Res, Taipei 11217, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Lin, Ting-Yi
Cho, Yi-Chun
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h-index: 0
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China Med Univ, Res Ctr Canc Biol, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Cho, Yi-Chun
Lai, Yo-Liang
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Grad Inst Biomed Sci, Taichung 40403, Taiwan
China Med Univ Hosp, Dept Radiat Oncol, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Lai, Yo-Liang
Wang, Shu-Chi
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h-index: 0
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Kaohsiung Med Univ, Dept Med Lab Sci & Biotechnol, Kaohsiung 80708, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Wang, Shu-Chi
Yeh, Hsin-Chih
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol, Kaohsiung 80708, Taiwan
Kaohsiung Municipal Tatung Hosp, Dept Urol, Kaohsiung 80145, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Yeh, Hsin-Chih
Chuu, Chih-Pin
论文数: 0引用数: 0
h-index: 0
机构:
Natl Hlth Res Inst, Inst Cellular & Syst Med, Miaoli 35053, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
机构:
China Med Univ, Res Ctr Canc Biol, Taichung 40403, Taiwan
China Med Univ, Grad Inst Biomed Sci, Taichung 40403, Taiwan
China Med Univ, PhD Program Canc Biol & Drug Discovery, Taichung 40403, Taiwan
Acad Sinica, Taichung 40403, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
Cheng, Wei-Chung
Li, Chia-Yang
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung 80708, TaiwanTaipei City Hosp, Renai Branch, Taipei 10629, Taiwan
机构:
Niigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, Japan
Niigata Univ, Grad Sch Med & Dent Sci, Dept Signal Transduct Res, Div Mol Oncol, Niigata, JapanNiigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, Japan
Hara, Noboru
Nishiyama, Tsutomu
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Niigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, JapanNiigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Urol, Niigata, Japan
机构:
St Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
Filippi, Luca
Palumbo, Barbara
论文数: 0引用数: 0
h-index: 0
机构:
Univ Perugia, Dept Med & Surg, Sect Nucl Med & Hlth Phys, Piazza Lucio Severi 1, I-06132 Perugia, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
Palumbo, Barbara
Bagni, Oreste
论文数: 0引用数: 0
h-index: 0
机构:
St Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
Bagni, Oreste
Frantellizzi, Viviana
论文数: 0引用数: 0
h-index: 0
机构:
Sapienza Univ Rome, Dept Radiol Sci Oncol & Anatomo Pathol, I-00185 Rome, ItalySt Maria Goretti Hosp, Nucl Med Unit, Via Antonio Canova, I-04100 Latina, Italy
机构:
Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, England
Univ Cambridge, Canc Res UK Cambridge Inst, Canc Res UK Cambridge Ctr, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England
Pinilla, Karen
Drewett, Lynsey M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England
Drewett, Lynsey M.
Lucey, Rebecca
论文数: 0引用数: 0
h-index: 0
机构:
Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England
Lucey, Rebecca
Abraham, Jean E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Cambridge, Precis Breast Canc Inst, Cambridge, England
Cambridge Univ Hosp, NHS Fdn Trust, Dept Oncol, Cambridge, England
Univ Cambridge, Canc Res UK Cambridge Inst, Canc Res UK Cambridge Ctr, Cambridge, EnglandUniv Cambridge, Precis Breast Canc Inst, Cambridge, England