Molecular pathways: CDK4 inhibitors for cancer therapy Journal Article
| Author: | Dickson, M. A. |
| Article Title: | Molecular pathways: CDK4 inhibitors for cancer therapy |
| Abstract: | Unrestrained growth is the hallmark of cancer, and disrupted cell-cycle regulation is, therefore, common. CDK4 is the key regulator of the G 1-S transition. In complex with cyclin D, CDK4 phosphorylates retinoblastoma protein (Rb) and drives cell-cycle progression, a process inhibited by pl6. The pl6-CDK4-cyclin D-Rb is aberrant in the majority of cancers and is, thus, a logical target for anticancer therapy. Previous attempts to block CDK4 with nonselective cyclin-dependent kinase (CDK) inhibitors led to toxicity and little efficacy. However, the recent development of selective CDK4 inhibitors launched the first successful efforts to target the pathway for cancer therapy. Three oral selective CDK4 inhibitors have entered clinical trials: palbociclib (PD0332991), LEEOll, and LY2835219. CDK4 inhibitors have in vitro activity against a broad range of cancers and in patients have shown antitumor activity in breast cancer, lymphoma, sarcoma, and other tumors. Major efforts are under way to develop biomarkers of response, understand potential mechanisms of resistance, and develop rational combinations of CDK4 inhibitors with chemotherapy and other targeted drugs. © 2014 American Association for Cancer Research. |
| Keywords: | cancer chemotherapy; treatment response; unclassified drug; fatigue; neutropenia; diarrhea; antineoplastic agent; cell cycle progression; protein p16; melanoma; infection; ovary cancer; breast cancer; mucosa inflammation; lung cancer; antineoplastic activity; tumor marker; fever; hematologic malignancy; enzyme phosphorylation; teratoma; flavopiridol; letrozole; anastrozole; cyclin dependent kinase inhibitor; cell cycle regulation; retinoblastoma protein; alopecia; gastrointestinal disease; everolimus; molecular model; liposarcoma; cyclin dependent kinase 4; fulvestrant; cyclin d; phosphatidylinositol 3 kinase inhibitor; antiproliferative activity; g1 phase cell cycle checkpoint; byl 719; human; priority journal; article; palbociclib; lee 011; ly 2835219 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 20 |
| Issue: | 13 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2014-07-01 |
| Start Page: | 3379 |
| End Page: | 3383 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-13-1551 |
| PROVIDER: | scopus |
| PUBMED: | 24795392 |
| DOI/URL: | |
| Notes: | Export Date: 1 August 2014 -- CODEN: CCREF -- Source: Scopus |
