Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have emerged as critical agents for cancer therapy. By inhibiting the catalytic activity of PARP enzymes and trapping them in the DNA, PARPis disrupt DNA repair, ultimately leading to cell death, particularly in cancer cells with homologous recombination repair deficiencies, such as those harboring BRCA mutations. This review delves into the mechanisms of action of PARPis in anticancer treatments, including the inhibition of DNA repair, synthetic lethality, and replication stress. Furthermore, the clinical applications of PARPis in various cancers and their adverse effects as well as their combinations with other therapies and the mechanisms underlying resistance are summarized. This review provides comprehensive insights into the role and mechanisms of PARP and PARPis in DNA repair, with a particular focus on the potential of PARPi-based therapies in precision medicine for cancer treatment.
Humans ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Neoplasms/genetics* ; DNA Repair/drug effects* ; Animals ; Antineoplastic Agents/therapeutic use*

OBJECTIVE: To investigate the relationship between Ig class switch recombination (CSR) and mismatch repair (MMR) protein, microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). METHODS: Forty cases of MALT lymphoma archived in the Department of Pathology, Jiading District Central Hospital, Shanghai University of Medicine & Health Sciences were selected as the observation group, and twenty cases of benign lymphoid tissue hyperplasia were as the control group. The expressions of IgG, IgM, IgD, and IgA in both groups were detected by immunohistochemical double staining, and MMR proteins including MLH1, MSH2, MSH6, and PMS2 in both groups were detected by immunohistochemistry. Multiplex fluorescence PCR capillary electrophoresis was used to detect microsatellite phenotype in tumor and adjacent tissues of the experimental group. RESULTS: In the observation group, the proportions of single Ig heavy chain expression (modeⅠ), negative expression (modeⅡ), and multiple expression (mode Ⅲ) were 65% (26/40), 27.5% (11/40), and 7.5% (3/40), respectively, while in the control group were 0 (0/20), 5% (1/20), and 95% (19/20). The proportion of Ig heavy chain expression mode Ⅰ+Ⅱ in the observation group was 92.5%, which was significantly higher than 5% in the control group (P < 0.01). In the observation group, partial deletion of MMR protein was observed in 3 cases (7.5%), including 2 cases of MSH6 deletion and 1 case of both MSH6 and PMS2 deletion. In the control group, there was 1 case (5%) with PMS2 deletion. There was no significant difference in the deletion rate of MMR protein between the two groups ( P >0.05). A total of 5 cases of microsatellite instability (MSI) were detected in the observation group, including 1 case of low-frequency MSI (MSI-L), 4 cases of high-frequency MSI (MSI-H), and 2 cases of MSI-H with MSH6 deletion. When the loss expression of MSI-H or MMR protein was counted as a positive result, the MSI-H rate detected by PCR capillary electrophoresis was 10% (4/40), which was slightly higher than the MMR protein deletion rate detected by immunohistochemistry (7.5%, 3/40), but there was no statistically significant difference between the two groups (P >0.05). The MMR protein deletion rates among the Ig heavy chain protein expression mode Ⅰ, mode Ⅱ, and mode Ⅲ groups were 0 (0/26), 18.2% (2/11), and 33.3% (1/3), respectively. There was a statistically significant difference in the constituent ratios among the three groups (P < 0.05). The MMR protein deletion rates among the MSS, MSI-L, and MSI-H groups were 2.9% (1/35), 0 (0/1), and 50% (2/4), respectively. There was a statistically significant difference in the constituent ratios among the three groups (P < 0.05). MMR protein deficiency was positively correlated with Ig heavy chain expression pattern and MSI ( r =0.41, P < 0.05; r =0.48, P < 0.05), but Ig heavy chain expression pattern was not correlated with MSI ( r =0.02, P >0.05). CONCLUSION Ig heavy chain CSR detection is helpful for the differential diagnosis of MALT lymphoma. Low frequency MMR protein deletion and MSI-H phenotype exist in MALT lymphoma, which may be of certain value for the study of its occurrence, development and clinical treatment.
Humans ; Lymphoma, B-Cell, Marginal Zone/genetics* ; DNA Mismatch Repair ; Immunoglobulin Class Switching ; DNA-Binding Proteins/metabolism* ; MutS Homolog 2 Protein ; Microsatellite Repeats ; Phenotype ; MutL Protein Homolog 1 ; Mismatch Repair Endonuclease PMS2 ; Male

Rectal cancer is one of the most common malignant tumors in China, with more than half of patients diagnosed at the locally advanced stage. Currently, the standard treatment for locally advanced rectal cancer (LARC) primarily involves neoadjuvant chemoradiotherapy followed by radical surgery. The advent of immune checkpoint inhibitors has revolutionized the neoadjuvant treatment landscape for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) rectal cancer. However, most rectal cancer patients exhibit mismatch repair-proficient/microsatellite stable (pMMR/MSS) status and show poor responsiveness to immunotherapy. In recent years, multiple studies have demonstrated that neoadjuvant short-course radiotherapy followed by chemotherapy and immunotherapy can improve the pathological complete response rate in pMMR/MSS LARC patients. Nevertheless, controversies persist regarding patient selection, efficacy evaluation, adverse event management, postoperative adjuvant therapy, and follow-up strategies. Considering the Colorectal Surgery Group of the Surgery Branch of the Chinese Medical Association, in collaboration with the Colorectal and Anal Surgery Committee of the Chinese Research Hospital Association, the Chinese Colorectal Cancer Clinical Research Collaborative Group, and related experts, has developed this consensus document by referencing domestic and international research advancements. The aim is to provide standardized guidance for the clinical application of this treatment approach.
Humans ; Rectal Neoplasms/genetics* ; Neoadjuvant Therapy ; Immunotherapy ; DNA Mismatch Repair ; Microsatellite Instability ; Consensus ; Combined Modality Therapy

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

The accumulation of deoxyribonucleic acid (DNA) oxidative damage mediated by reactive oxygen species (ROS) is closely associated with liver diseases. 8-Oxoguanine (8-OxoG), a prevalent DNA oxidation product, plays a significant role in liver disease progression. The base excision repair (BER) pathway, comprising over 30 proteins including 8-OxoG DNA glycosylase1 (OGG1), MutY homolog (MUTYH), and MutT homolog protein 1 (MTH1), is responsible for the clearance and mismatch repair of 8-OxoG. Abnormally high levels of 8-OxoG and dysregulated expression and function of 8-OxoG repair enzymes contribute to the onset and development of liver diseases. Consequently, targeting the 8-OxoG production and repair system with agonists or inhibitors may offer a promising approach to liver disease treatment. This review summarizes the impact of 8-OxoG accumulation and dysregulated repair enzymes on various liver diseases, including viral liver disease, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), cholestatic liver disease (CLD), liver fibrosis, cirrhosis, and liver cancer. Additionally, we review natural constituents as potential therapeutic agents that regulate 8-OxoG production, repair enzymes, and repair system-related signal pathways in oxidative damage-induced liver diseases.
Humans ; Liver Diseases/genetics* ; Biological Products/pharmacology* ; DNA Repair/drug effects* ; Guanine/metabolism* ; Animals ; Disease Progression ; DNA Damage ; Oxidative Stress

DNA double-strand breaks represent a common type of serious DNA damage in living organisms, causing instability of the genome and leading to cell death. Homologous recombination and non-homologous end-joining (NHEJ) are the two main ways to repair DNA double-strand breaks. The core components involved in the NHEJ pathway are highly conserved in both yeast and humans. A few bacteria such as Mycobacterium, Pseudomonas aeruginosa, and Bacillus subtilis also have the NHEJ mechanism. NHEJ plays a key role in the double strand repair of Mycobacterium in latency. This paper summarizes the mechanism and important components of NHEJ in Mycobacterium, introduces the application of NHEJ in gene editing, and reviews the research progress of the NHEJ pathway in Mycobacterium. We hope to bring new insights into the molecular mechanism and provide clues for the application of NHEJ in Mycobacterium.
DNA End-Joining Repair/physiology* ; Gene Editing/methods* ; Mycobacterium/physiology* ; DNA Breaks, Double-Stranded ; Humans

Objective: To investigate the correlation between adjuvant chemotherapy with platinum-containing regimens and DNA damage repair (DDR) defects in early-stage triple negative breast cancer (TNBC), and to provide a basis for precise treatment of TNBC. Methods: Next-generation sequencing (NGS) testing was performed on postoperative breast cancer specimens selected from the Cancer Hospital of Chinese Academy of Medical Sciences from June 2009 to October 2015 to analyze the correlation between DDR gene variants and the efficacy of adjuvant chemotherapy with TNBC platinum-containing regimens, and thus to screen the superior population for adjuvant chemotherapy with TNBC platinum-containing regimens. The study used t-test, χ(2) test, Fisher's exact test, rank sum test and multifactorial logistic analysis to assess the associations between mutated genes and clinicopathological characteristics and prognosis, and Log-rank test and Cox proportional risk model were used for survival and correlation analysis. Results: NGS results were successfully obtained in 149 patients (74 in the platinum-containing group and 75 in the platinum-free group), with a 97.3% (145/149) DDR gene mutation rate and a median number of 4 mutations in all patients. 5-year disease-free survival (DFS) was 85.4% and 75.0% for patients with DDR gene mutations and DDR gene wild-type, respectively, without statistical difference (P=0.825). The 5-year DFS rates of patients with homologous recombination repair (HRR) pathway mutation were 84.6% in platinum-containing (TCb) group and 84.9% in platinum-free (EC-T) group (P=0.554), respectively. The 5-year DFS rates of patients with and without mutations in the platinite-containing HRR pathway were 84.9% and 85.0%, respectively (P=0.751). The number of DDR pathways with mutations and the number of DDR gene mutations were not associated with prognosis (both P>0.05). PIK3CA mutation patients in TCb group had a worse prognosis than wild-type patients (5-year DFS were 71.4% and 88.1%, P=0.037), and KMT2D mutation patients in EC-T group had a worse prognosis than wild-type patients (5-year DFS were 76.9% and 86.8%, P=0.039). Conclusions: DDR gene variation is common in TNBC, more clinical studies are needed to prove whether DDR variation can serve as effective biomarkers for treatment with platinum.
Humans ; Triple Negative Breast Neoplasms/pathology* ; DNA Repair ; Mutation ; Combined Modality Therapy ; DNA Damage

Humans ; Small Cell Lung Carcinoma/drug therapy* ; Lung Neoplasms/drug therapy* ; Colonic Neoplasms/drug therapy* ; Microsatellite Instability ; DNA Mismatch Repair ; Colorectal Neoplasms

Objective: To investigate the correlation between adjuvant chemotherapy with platinum-containing regimens and DNA damage repair (DDR) defects in early-stage triple negative breast cancer (TNBC), and to provide a basis for precise treatment of TNBC. Methods: Next-generation sequencing (NGS) testing was performed on postoperative breast cancer specimens selected from the Cancer Hospital of Chinese Academy of Medical Sciences from June 2009 to October 2015 to analyze the correlation between DDR gene variants and the efficacy of adjuvant chemotherapy with TNBC platinum-containing regimens, and thus to screen the superior population for adjuvant chemotherapy with TNBC platinum-containing regimens. The study used t-test, χ(2) test, Fisher's exact test, rank sum test and multifactorial logistic analysis to assess the associations between mutated genes and clinicopathological characteristics and prognosis, and Log-rank test and Cox proportional risk model were used for survival and correlation analysis. Results: NGS results were successfully obtained in 149 patients (74 in the platinum-containing group and 75 in the platinum-free group), with a 97.3% (145/149) DDR gene mutation rate and a median number of 4 mutations in all patients. 5-year disease-free survival (DFS) was 85.4% and 75.0% for patients with DDR gene mutations and DDR gene wild-type, respectively, without statistical difference (P=0.825). The 5-year DFS rates of patients with homologous recombination repair (HRR) pathway mutation were 84.6% in platinum-containing (TCb) group and 84.9% in platinum-free (EC-T) group (P=0.554), respectively. The 5-year DFS rates of patients with and without mutations in the platinite-containing HRR pathway were 84.9% and 85.0%, respectively (P=0.751). The number of DDR pathways with mutations and the number of DDR gene mutations were not associated with prognosis (both P>0.05). PIK3CA mutation patients in TCb group had a worse prognosis than wild-type patients (5-year DFS were 71.4% and 88.1%, P=0.037), and KMT2D mutation patients in EC-T group had a worse prognosis than wild-type patients (5-year DFS were 76.9% and 86.8%, P=0.039). Conclusions: DDR gene variation is common in TNBC, more clinical studies are needed to prove whether DDR variation can serve as effective biomarkers for treatment with platinum.
Humans ; Triple Negative Breast Neoplasms/pathology* ; DNA Repair ; Mutation ; Combined Modality Therapy ; DNA Damage

Humans ; Small Cell Lung Carcinoma/drug therapy* ; Lung Neoplasms/drug therapy* ; Colonic Neoplasms/drug therapy* ; Microsatellite Instability ; DNA Mismatch Repair ; Colorectal Neoplasms