Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives
Cyclin-dependent kinases (CDKs) are generally involved in the progression of cell cycle and cell division in normal cells, while abnormal activations of CDKs are deemed to be a driving force for accelerating cell proliferation and tumorigenesis. Therefore, CDKs have become ideal therapeutic targets...
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MDPI AG
2024-10-01
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| author | Yongqin Liu Yiying Deng Chang Yang Hua Naranmandura |
| author_facet | Yongqin Liu Yiying Deng Chang Yang Hua Naranmandura |
| author_sort | Yongqin Liu |
| collection | DOAJ |
| description | Cyclin-dependent kinases (CDKs) are generally involved in the progression of cell cycle and cell division in normal cells, while abnormal activations of CDKs are deemed to be a driving force for accelerating cell proliferation and tumorigenesis. Therefore, CDKs have become ideal therapeutic targets for cancer treatment. The U.S FDA has approved three CDK4/6 inhibitors (CDK4/6is) for the treatment of patients with hormone receptor-positive (HR<sup>+</sup>) or human epidermal growth factor receptor 2-negative (HER2<sup>−</sup>) advanced or metastatic breast cancer, and these drugs showed impressive results in clinics. Besides cell-cycle arrest, there is growing evidence that CDK4/6is exert paradoxical roles on cancer treatment by altering the immune system. Indeed, clinical data showed that CDK4/6is could change the immune system to exert antitumor effects, while these changes also caused tumor resistance to CDK4/6i. However, the molecular mechanism for the regulation of the immune system by CDK4/6is is unclear. In this review, we comprehensively discuss the paradoxical immunological effects of CDK4/6is in cancer treatment, elucidating their anticancer mechanisms through immunomodulatory activity and induction of acquired drug resistance by dysregulating the immune microenvironment. More importantly, we suggest a few strategies including combining CDK4/6is with immunotherapy to overcome drug resistance. |
| format | Article |
| id | doaj-art-3c3dead5307b4d1592dfa476970c94d8 |
| institution | Kabale University |
| issn | 2306-5354 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Bioengineering |
| spelling | doaj-art-3c3dead5307b4d1592dfa476970c94d82024-11-26T17:51:52ZengMDPI AGBioengineering2306-53542024-10-011111108410.3390/bioengineering11111084Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and PerspectivesYongqin Liu0Yiying Deng1Chang Yang2Hua Naranmandura3Department of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, ChinaCyclin-dependent kinases (CDKs) are generally involved in the progression of cell cycle and cell division in normal cells, while abnormal activations of CDKs are deemed to be a driving force for accelerating cell proliferation and tumorigenesis. Therefore, CDKs have become ideal therapeutic targets for cancer treatment. The U.S FDA has approved three CDK4/6 inhibitors (CDK4/6is) for the treatment of patients with hormone receptor-positive (HR<sup>+</sup>) or human epidermal growth factor receptor 2-negative (HER2<sup>−</sup>) advanced or metastatic breast cancer, and these drugs showed impressive results in clinics. Besides cell-cycle arrest, there is growing evidence that CDK4/6is exert paradoxical roles on cancer treatment by altering the immune system. Indeed, clinical data showed that CDK4/6is could change the immune system to exert antitumor effects, while these changes also caused tumor resistance to CDK4/6i. However, the molecular mechanism for the regulation of the immune system by CDK4/6is is unclear. In this review, we comprehensively discuss the paradoxical immunological effects of CDK4/6is in cancer treatment, elucidating their anticancer mechanisms through immunomodulatory activity and induction of acquired drug resistance by dysregulating the immune microenvironment. More importantly, we suggest a few strategies including combining CDK4/6is with immunotherapy to overcome drug resistance.https://www.mdpi.com/2306-5354/11/11/1084CDK4/6 inhibitorimmunomodulatory effectdrug resistanceimmune microenvironmentimmunotherapy |
| spellingShingle | Yongqin Liu Yiying Deng Chang Yang Hua Naranmandura Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives Bioengineering CDK4/6 inhibitor immunomodulatory effect drug resistance immune microenvironment immunotherapy |
| title | Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives |
| title_full | Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives |
| title_fullStr | Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives |
| title_full_unstemmed | Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives |
| title_short | Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives |
| title_sort | double faced immunological effects of cdk4 6 inhibitors on cancer treatment challenges and perspectives |
| topic | CDK4/6 inhibitor immunomodulatory effect drug resistance immune microenvironment immunotherapy |
| url | https://www.mdpi.com/2306-5354/11/11/1084 |
| work_keys_str_mv | AT yongqinliu doublefacedimmunologicaleffectsofcdk46inhibitorsoncancertreatmentchallengesandperspectives AT yiyingdeng doublefacedimmunologicaleffectsofcdk46inhibitorsoncancertreatmentchallengesandperspectives AT changyang doublefacedimmunologicaleffectsofcdk46inhibitorsoncancertreatmentchallengesandperspectives AT huanaranmandura doublefacedimmunologicaleffectsofcdk46inhibitorsoncancertreatmentchallengesandperspectives |