Immunotherapy for prostate cancer: current status and future perspectives / 现代泌尿外科杂志

As an emerging cancer treatment modality, immunotherapy has shown promising efficacy in a variety of solid tumors, but it has failed to achieve a breakthrough in the treatment of prostate cancer.This review aims to provide an overview of the current applications of immunotherapy for prostate cancer, including immune-checkpoint inhibitors, cancer vaccines and chimeric antigen receptor T-cell (CAR-T), briefly describe the mechanisms of various immunotherapy modalities, summarize the results of clinical trials, and discuss the challenges and prospects.

Mismatch repair gene germline mutations in patients with prostate cancer / 浙江大学学报·医学版

OBJECTIVES@#To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics.@*METHODS@#Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR+ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR+MMR－ group) and patients without DDR gene germline pathogenic mutation (DDR－ group).@*RESULTS@#Thirteen (1.52%) MMR+ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR－ group, MMR+ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR+ group, DDR+MMR－ group and DDR－ group, respectively. The time to castration resistance in MMR+ group was significantly shorter than that in DDR+MMR－ group and DDR－ group (both P<0.01), while there was no significant difference between DDR+MMR－ group and DDR－ group (P>0.05).@*CONCLUSIONS@#MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.

Prostate cancer with homologous recombination repair gene mutations and PARP inhibitors: clinical progress / 中华泌尿外科杂志

DNA damage repair gene mutations are prevalent in advanced prostate cancer. Among these, mutations in homologous recombination repair genes could impair the ability of cell to restore the DNA double-strand break, which can be exploited by Poly-ADP-ribose polymerase (PARP) inhibitors through synthetic lethality and result in cell death. The phase Ⅲ study " PROfound" showed that the PAPR inhibitor Olaparib could significantly improve the survival of patients with homologous recombination repair gene mutations compared with novel hormone agents, starting the era of targeted, precise and individualized treatment based on genetic profile detection for prostate cancer treatment.