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Overcoming Endocrine Resistance in Hormone-Receptor Positive Advanced Breast Cancer-The Emerging Role of CDK4/6 Inhibitors.
| Content Provider | Semantic Scholar |
|---|---|
| Author | O'Sullivan, Ciara C. |
| Copyright Year | 2015 |
| Abstract | Dysregulation of the cyclin D and cyclin-dependent kinase (CDK) pathway in cancer cells may inhibit senescence and promote cellular proliferation. By using various different mechanisms, malignant cells may increase cyclin D-dependent activity. The cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway controls the cell cycle restriction point, and is commonly dysregulated in breast cancer; making it a rational target for anticancer therapy. To date, three oral highly selective cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are in various stages of clinical development: PD0332991 (palbociclib), LEE011 (ribociclib) and LY2835219 (abemaciclib). Results from phase I, II and III trials in hormone-receptor (HR)-positive breast cancer have been encouraging, demonstrating convincing efficacy and a tolerable side-effect profile (mainly uncomplicated neutropenia). This article will review the preclinical and clinical development of the CDK4/6i, as well as reviewing the existing preclinical evidence regarding combination of these agents with chemotherapy and other targeted therapies. Future and ongoing clinical trials, which may expand the potential application of these agents, will also be discussed. In summary, CDK4/6i are exciting compounds which may change the therapeutic landscape of HR-positive breast cancer. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://clinmedjournals.org/articles/ijccr/international-journal-of-cancer-and-clinical-research-ijccr-2-029.pdf |
| PubMed reference number | 26726315v1 |
| Volume Number | 2 |
| Issue Number | 4 |
| Journal | International journal of cancer and clinical research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Breast Carcinoma CDK6-associated protein p18 Cell Cycle Cell Proliferation Cyclin D Cyclin-Dependent Kinases Cyclins Gonadorelin LEE011 LY2835219 Malignant neoplasm of breast Mammary Neoplasms Neutropenia PD 0332991 Review [Publication Type] Therapeutic procedure abemaciclib cancer cell heart rate palbociclib receptor ribociclib |
| Content Type | Text |
| Resource Type | Article |
