Figure 4.

Potential for clinical use of CDK12 as a biomarker and/or therapeutic target. (A) CDK12 mutations that confer loss of function have been reported to promote genomic instability, rendering cancer cells more susceptible to PARP/CHK inhibitors. (B) On the other hand, CDK12 mutations that cause gain of function (e.g. amplification) could theoretically potentiate cancer cell survival by promoting expression of DNA damage repair genes. Though there are currently few reports of this, such a situation would enable use of CDK12 as a biomarker of drug response/clinical outcome, or as a drug target. (C) In cases where CDK12 is not necessarily mutated, CDK12 can enable tumor progression driven by genes such as MYC and EWS/FLI. These synthetic lethal interactions also provide an opportunity for therapeutic targeting.