SRINAGARIND MEDICAL JOURNAL

Volume 36, No. 02, Month MARCH, Year 2021, Pages 229 - 239

Cyclin dependent kinases 46 inhibitors a new hope for breast cancer therapy

Charupong Saengboonmee, Thanachai Sanlung, Sopit Wongkham

Abstract Download PDF

The limitless of self-renewal and replication of cancer cells, one of cancer hallmarks, is supported by various molecular mechanisms. Overexpression of cyclins and cyclin-dependent kinases, a group of cell cycle machinery proteins, is one of the underlying mechanisms that promotes cell proliferation in several cancers, especially in breast cancer. Breast cancer is the highest prevalent cancer among female patients in Thailand and globally. Many studies revealed the overexpression of cyclin D1, a partner of cyclin-dependent kinase 4/6 (CDK4/6), in more than 30% of breast cancer cases. These proteins are indicated to be essential for survival of breast cancer cells but are disputable for normal mammary cells. These findings, thus, led to the development of CDK4/6 inhibitors which arrest the cell cycle at G1 phase and inhibit cell division. These inhibitors have been tested for their efficacy both preclinical studies in breast cancer cells and clinical trials in breast cancer patients. Patients who supplemented with these drugs had almost double longer survival times compared with those who received the placebo. The efficiency of CDK4/6 inhibitors, hence, urged the approval and implementation of the CDK4/6 inhibitors into the clinical practice. The discovery of CDK4/6 inhibitors is one of the successful translations of basic medical research to the clinical study which finally implemented in the clinical practice of breast cancer treatment at present.

Keywords

Breast cancer; cell cycle; cyclin; cyclin dependent kinase

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