CDK12 is among the most frequently mutated cyclindependent kinases (CDKs) in various cancers, including prostate, ovarian, breast, esophageal, bladder, and colon cancers. 1 Specifically, biallelic aberrations of CDK12 occur in 3%-7% of metastatic castration-resistant prostate cancer (mCRPC) cases and correlate with poor prognosis. 1 One of the most well-studied functions of CDK12 is its orchestration of transcription initiation and elongation through cyclin K-dependent Ser2 phosphorylation of RNA polymerase II, 2 and therefore CDK12 is important in regulating the expression of long genes or genes with high exon numbers, especially DNA damage response (DDR)-related genes such as BRCA1, ATR, FANCI, and FANCD21. 3 As a result, CDK12-deficient cancers are commonly characterized by focal tandem duplications (FTDs) and various features of genome instability. 4,5 Because FTDs often generate a large amount of neoantigens, it has been suggested that CDK12-deficient tumours may be more sensitive to immunotherapy. 5 However, studies of immune checkpoint blockade therapy have shown only limited effects in mCRPC patients harbouring CDK12 mutations. 6 Likewise, despite the observed sensitization of CDK12-deficient Wei-Ling Tu andMu-En Wang contributed equally.