Recent advances of highly selective CDK4/6 inhibitors in breast cancer
Abstract Uncontrolled cell division is the hallmark of cancers. Full understanding of cell cycle regulation would contribute to promising cancer therapies. In particular, cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell proliferation by combination with cyclin D, draw more an...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-04-01
|
| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-017-0467-2 |
| _version_ | 1811301884459220992 |
|---|---|
| author | Hanxiao Xu Shengnan Yu Qian Liu Xun Yuan Sridhar Mani Richard G. Pestell Kongming Wu |
| author_facet | Hanxiao Xu Shengnan Yu Qian Liu Xun Yuan Sridhar Mani Richard G. Pestell Kongming Wu |
| author_sort | Hanxiao Xu |
| collection | DOAJ |
| description | Abstract Uncontrolled cell division is the hallmark of cancers. Full understanding of cell cycle regulation would contribute to promising cancer therapies. In particular, cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell proliferation by combination with cyclin D, draw more and more attention. Subsequently, extensive studies were carried out to explore drugs inhibiting CDK4/6 and assess the efficacy and safety of these drugs in cancer, especially breast cancer. Due to the insuperable adverse events and the less activity observed in vivo, the drug development of the initial pan-CDK inhibitor flavopiridol was consequently discontinued, and then highly specific inhibitors were extensively researched and developed, including palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Food and Drug Administration has approved palbociclib and ribociclib for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer, and recent clinical trial data suggest that palbociclib significantly improved clinical outcome when combined with letrozole or fulvestrant. Besides, the favorable effects of abemaciclib on prolonging survival of breast cancer patients have also been observed in clinical trials both for single-agent and combination strategy. In this review, we outline the preclinical and clinical advancement of these three orally bioavailable and highly selective CDK4/6 inhibitors in breast cancer. |
| first_indexed | 2024-04-13T07:18:00Z |
| format | Article |
| id | doaj.art-7b957c61008b41448a050d620a1346b2 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-13T07:18:00Z |
| publishDate | 2017-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-7b957c61008b41448a050d620a1346b22022-12-22T02:56:42ZengBMCJournal of Hematology & Oncology1756-87222017-04-0110111210.1186/s13045-017-0467-2Recent advances of highly selective CDK4/6 inhibitors in breast cancerHanxiao Xu0Shengnan Yu1Qian Liu2Xun Yuan3Sridhar Mani4Richard G. Pestell5Kongming Wu6Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyAlbert Einstein Cancer Center, Albert Einstein College of MedicinePennsylvania Center for Cancer and Regenerative MedicineDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyAbstract Uncontrolled cell division is the hallmark of cancers. Full understanding of cell cycle regulation would contribute to promising cancer therapies. In particular, cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell proliferation by combination with cyclin D, draw more and more attention. Subsequently, extensive studies were carried out to explore drugs inhibiting CDK4/6 and assess the efficacy and safety of these drugs in cancer, especially breast cancer. Due to the insuperable adverse events and the less activity observed in vivo, the drug development of the initial pan-CDK inhibitor flavopiridol was consequently discontinued, and then highly specific inhibitors were extensively researched and developed, including palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Food and Drug Administration has approved palbociclib and ribociclib for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer, and recent clinical trial data suggest that palbociclib significantly improved clinical outcome when combined with letrozole or fulvestrant. Besides, the favorable effects of abemaciclib on prolonging survival of breast cancer patients have also been observed in clinical trials both for single-agent and combination strategy. In this review, we outline the preclinical and clinical advancement of these three orally bioavailable and highly selective CDK4/6 inhibitors in breast cancer.http://link.springer.com/article/10.1186/s13045-017-0467-2Breast cancerCDK4/6 inhibitorsPalbociclibRibociclibAbemaciclibSafety |
| spellingShingle | Hanxiao Xu Shengnan Yu Qian Liu Xun Yuan Sridhar Mani Richard G. Pestell Kongming Wu Recent advances of highly selective CDK4/6 inhibitors in breast cancer Journal of Hematology & Oncology Breast cancer CDK4/6 inhibitors Palbociclib Ribociclib Abemaciclib Safety |
| title | Recent advances of highly selective CDK4/6 inhibitors in breast cancer |
| title_full | Recent advances of highly selective CDK4/6 inhibitors in breast cancer |
| title_fullStr | Recent advances of highly selective CDK4/6 inhibitors in breast cancer |
| title_full_unstemmed | Recent advances of highly selective CDK4/6 inhibitors in breast cancer |
| title_short | Recent advances of highly selective CDK4/6 inhibitors in breast cancer |
| title_sort | recent advances of highly selective cdk4 6 inhibitors in breast cancer |
| topic | Breast cancer CDK4/6 inhibitors Palbociclib Ribociclib Abemaciclib Safety |
| url | http://link.springer.com/article/10.1186/s13045-017-0467-2 |
| work_keys_str_mv | AT hanxiaoxu recentadvancesofhighlyselectivecdk46inhibitorsinbreastcancer AT shengnanyu recentadvancesofhighlyselectivecdk46inhibitorsinbreastcancer AT qianliu recentadvancesofhighlyselectivecdk46inhibitorsinbreastcancer AT xunyuan recentadvancesofhighlyselectivecdk46inhibitorsinbreastcancer AT sridharmani recentadvancesofhighlyselectivecdk46inhibitorsinbreastcancer AT richardgpestell recentadvancesofhighlyselectivecdk46inhibitorsinbreastcancer AT kongmingwu recentadvancesofhighlyselectivecdk46inhibitorsinbreastcancer |