Open AccessMechanisms of Resistance to CDK4/6 Inhibitors in Breast Cancer and Potential Biomarkers of Response
Author(s) -
Cristina Guarducci,
Martina Bonechi,
Giulia Boccalini,
Matteo Benelli,
Emanuela Risi,
Angelo Di Leo,
Luca Malorni,
Ilenia Migliaccio
Publication year - 2017
Publication title -
breast care
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.767
H-Index - 30
eISSN - 1661-3805
pISSN - 1661-3791
DOI - 10.1159/000484167
Subject(s) - palbociclib , medicine , breast cancer , metastatic breast cancer , oncology , acquired resistance , clinical trial , cancer , bioinformatics , biology
Randomized clinical trials demonstrated that CDK4/6 inhibitors are highly effective in patients with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer in combination with endocrine therapy. The use of CDK4/6 inhibitors in clinics is becoming common for patients with HR+/HER2- metastatic breast cancer and will certainly increase in the near future. However, patients might show de novo or acquired resistance to these drugs. Molecular alterations have been suggested as determinants for de novo resistance to CDK4/6 inhibitors, but have never been validated in a clinical setting. In addition, molecular mechanisms of acquired resistance to palbociclib have been analyzed only in preclinical studies. Here we review the current knowledge on the available preclinical data about the mechanisms of de novo and acquired resistance to CDK4/6 inhibitors in breast cancer, and clinical data about potential biomarkers of response.