Table 1.
Overview of therapeutic sensitivity of tumours/tissues with indicated phenotype and CDK12 status
| Tissue/tumour | CDK12 status | Related phenotype | Drug sensitivity | References |
|---|---|---|---|---|
| Breast (TNBC) | WT | HR-proficient | CDK12 inhibitors (dinaciclib, SR-4835) + PARP inhibitors (olaparib) or DNA-damaging drugs (platinum-based, doxorubicin, irinotecan) | (42,116) |
| Ovarian (HGSOC) and breast | Inactivating mutations; shRNA/siRNA depletion of WT | HR deficiency | PARP inhibitors, DNA-damaging drugs | (10,82,83) |
| Breast (HER2-positive) | Genomic disruption (out-of-frame rearrangements due to breakpoint of HER2 amplicon) | HR deficiency | PARP inhibitors | (108,109) |
| Metastatic osteosarcoma | WT | HR-proficient | CDK12 inhibitors (dinaciclib, THZ531) | (117) |
| Foreskin fibroblasts | siRNA depletion of WT | c-MYC overexpression | (103) | |
| Neuroblastoma and ovarian | WT | N-MYC/c-MYC amplification | CDK inhibitors (roscovitine, CR8, THZ1) | (104,124) |
| Breast (trastuzumab- resistant/sensitive HER2-positive) | Amplified | HER2 amplification | CDK12 inhibitor (dinaciclib, THZ531) | (110) |
| Hepatocellular carcinoma (sorafenib-treated) | WT | EGFR/HER3 and PI3K/AKT activation | CDK12 inhibitor (THZ531) | (126) |
| Ewing sarcoma | WT | EWS/FLI expression | CDK12 inhibitor (THZ531) + PARP inhibitors (olaparib) | (128) |
| Cancer cell lines (colon, ovarian) | siRNA depletion of WT | Replication stress | CHK1 inhibitors | (129) |
| Prostate (mCRPC) | Biallelic loss-of-function mutations | Focal tandem duplications, high neoantigen load | Immune checkpoint (PD-1) inhibitors | (88,94,132) |
| Ovarian (HGSOC) | siRNA depletion of WT | BRCA1 deficiency (HR deficiency-independent metabolic reprogramming) | Metabolic inhibitors | (135) |
WT = wild-type CDK12.