Title:Synthesis and Clinical Development of Palbociclib: An Overview
Volume: 18
Issue: 1
Author(s): Debabrata Konar, Saurabh Maru, Subhabrata Kar and Kapil Kumar*
Affiliation:
- National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Mohali, Punjab-160062,India
Keywords:
Palbociclib, Breast cancer, CDK4, CDK6, Clinical trial, carcinoma.
Abstract: Breast cancer is the second most commonly identified cancer in women in the United
States after skin cancer. The past few years have seen a substantial increase in breast cancer awareness
campaigns and active research in fields of diagnosis and targeted therapy. These factors have led
to a better mechanistic understanding of the disease, detection at earlier stages, and a more personalized
approach to treatment, ultimately causing a crucial increase in the survival rates after detection.
However, with the advances in treatment, cases of patients developing primary resistance and acquired
resistance are increasing. Most of the breast cancers which develop resistance to therapy are
ER+ and are typically treated with tamoxifen and fulvestrant. These drugs either lower the levels of
estrogen or inhibit the receptors for estrogen and prevent the tumor from spreading. Around one-third
of women treated with these drugs develop resistance to them, lowering their chances of survival.
This has directed the search for newer drug therapies to target advanced breast cancer and resistance.
One of these efforts has resulted in the development of Palbociclib, a first in class inhibitor of cyclin
dependent kinases 4 and 6 (CDK4 and CDK6), which was granted accelerated approval from the
FDA for combination therapy in postmenopausal women with ER+, HER2- metastatic breast cancer.
This review is focused on the various aspects of “Palbociclib” including its synthesis, molecular
modeling studies, and efficacy and safety profile with data obtained from various clinical trials.