In 2018, the first PARP inhibitor Olaparib and the injectable immune checkpoint inhibitor Pabolizumab were marketed in China, and the treatment of prostate cancer patients in China officially entered the era of precision medicine. “Consensus of experts on genetic testing for prostate cancer patients in China (2018 edition) ” calls for the clinical application of NGS detection to be valued:
For the different genes, based on the level of evidence the consensus divided them into four levels ABCD. The germline mutations of BRCA1/2 and MMR genes were classified as class A, and the somatic + embryo series of these genes including BRCA1/2, ATM, PALB2, FANCA and MMR genes in mCRPC were also classified as class A. HR genes such as BRCA1/2 and ATM were classified into grade A based on the data that PARP inhibitors have been enriching the therapeutic effect of HRD in recent years. For dMMR/MSI-H patients, the US FDA approved the application of Pabolizumab in unresectable or metastatic solid tumors(dMMR/MSI-H) in May 2017.
The detection of these two kinds of genes has become a demand for prostate cancer treatment.
In addition, studies found that patients with prostate cancer also include gene mutations in AR, PTEN, TP53, PI3K signaling pathways (PIK-3CA, PIK3R1, AKT1 and AKT3), WNT signaling pathways (APC, CTNNB1 and RNF43), and cell cycle pathways (RB1, CCND1, CDKN2A/B, CDKN1B, and CDK4), MAPK signaling pathways (BRAF, HRAS, and K-ras), and chromosomal remodeling signaling pathways (KMT2A, KMT2C, KMT2D, and KDM6A). The development of drugs for these genes and the clinical application of related targeted drugs in prostate cancer have received extensive attention, and we look forward to further clinical validation.
In addition to drug use, the detection of genes such as HOXB13 in patients with familial inherited prostate cancer and family management will also benefit from genetic testing during diagnosis and treatment.