Cyclin-dependent kinase 12 (also known as CRK7 (CDC2-related protein kinase 7); CRKR; CRKRS; hCDK12) is a protein kinase that in humans is encoded by the CDK12 gene. This enzyme is a member of cyclin-dependent kinase protein family. (https://en.wikipedia.org/wiki/CDK12)

Role in human Cancer

• Ovarian cancer:
  • Putative functional inactive mutations (Nature 2011)
  • Regulation of PARP inhibitor sensitivity: low CDK12 --> PARP inhibitor sensitive (Cancer Res, 2013; JBC 2014)
• Breast cancer:
  • Genomic disruption in breast cancer (J Pathol 2014)), fusion with LASP1, HER2 correlation, PARP1/2 resistance
  • Regulation of endocrine therapy in breast cancer (Carcinogenesis 2009): low CDK12 --> anti-estrogen resistant, MAPK activation

ERBB2 근처에 있어 종종 같이 amplification 됨. 변이가 있는 경우, DNA repair 관련 유전자들의 발현이 아니되면서, DNA damage response 능력이 감소하면서 암이 된다. PARP inhibitor를 주면 Synthetic lethality 효과가 있다.

관련 기사

• "암세포 전이 유전자 CDK12, 염색체 분리도 관여" 2019-04-03: CDK12를 억제하는 표적 약물을 개발하면, 이 유전자의 돌연변이가 없는 대다수 암에 화학치료제나 면역치료제를 효과적으로 쓸 수 있다.

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