title: Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data.
abstract: For millions of women, breast cancer remains a potentially life-endangering diagnosis. With advances in research, new therapies targeted to tumor biology are emerging to treat the most common form of this disease. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of therapeutic agents that have the potential to improve the outcomes of patients with hormone receptor-positive (HR(+)) breast cancer. Three CDK 4/6 inhibitors have been investigated for the treatment of HR(+) breast cancer, including palbociclib (PD 0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Palbociclib recently received accelerated Food and Drug Administration approval for the treatment of HR(+) metastatic breast cancer in combination with letrozole, and recent data suggest improved outcome when combined with fulvestrant. In this article, the mechanism of action of CDK 4/6 inhibitors, preclinical studies on their efficacy, ongoing clinical trials in breast cancer, and toxicity profiles are reviewed.
authors: Division of Hematology-Oncology, University of California, San Francisco, San Francisco, CA.
authors: Neelima
authors: N
authors: Vidula
authors: Division of Hematology-Oncology, University of California, San Francisco, San Francisco, CA. Electronic address: Hope.Rugo@ucsf.edu.
authors: Hope S
authors: HS
authors: Rugo
mesh_terms: D000631:Aminopyridines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011725:Pyridines; C000590451:abemaciclib; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; C500026:palbociclib; C000589651:ribociclib
keywords: Abemaciclib; CDK 4/6 inhibitors; Hormone receptor-positive breast cancer; Palbociclib; Ribociclib