Angel or Devil ? - CDK8 as the new drug target
Dan Wu1, Zhaoyan Zhang2, Xing Chen2
1School of Biological Engineering, Hefei Technology College, Hefei, 238000, PR China.
European Journal of Medicinal Chemistry
|December 1, 2020
Summary
Cyclin-dependent kinase 8 (CDK8) is crucial in cancer development and treatment resistance, acting as both a carcinogen and tumor suppressor. Understanding its complex roles is key for developing novel CDK8 inhibitors for cancer and inflammatory diseases.
Area of Science:
- Molecular Biology
- Oncology
- Pharmacology
Background:
- Cyclin-dependent kinase 8 (CDK8) is integral to transcription regulation via kinase module formation and transcription factor phosphorylation.
- CDK8 is implicated in cancer initiation, progression, and resistance to therapies like radiotherapy and chemotherapy.
- Its dual role as a carcinogen and tumor suppressor, alongside involvement in inflammation and immune disorders, highlights its complex biological functions.
Purpose of the Study:
- To summarize current research on CDK8's physiological and pathogenic mechanisms.
- To review the development status of compounds targeting CDK8.
- To evaluate CDK8's therapeutic potential and guide future research.
Main Methods:
- Literature review of studies on CDK8.
- Analysis of CDK8's role in various cancers and diseases.
- Compilation of data on CDK8 inhibitor development.
Main Results:
- CDK8's involvement in cancer cell invasion, metastasis, and drug resistance is confirmed.
- Evidence supports CDK8's dual role, acting as both an oncogene and a tumor suppressor depending on context.
- CDK8 shows promise as a therapeutic target for cancer, inflammation, and immune system disorders.
Conclusions:
- CDK8 is a significant therapeutic target with potential applications in oncology and immunology.
- Further research into CDK8's complex functions is needed to optimize inhibitor development.
- This review provides a foundation for evaluating CDK8 as a viable therapeutic strategy.
Related Concept Videos
02:15M-Cdk Drives Transition Into Mitosis
6.0K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.0K
02:34Inhibition of Cdk Activity
5.4K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
02:39Positive Regulator Molecules
6.3K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.3K
01:45Positive Regulator Molecules
124.1K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
124.1K
00:50Anaphase Promoting Complex
3.1K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.1K
02:57Targeted Cancer Therapies
8.2K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.2K