Novel 2,6,9-Trisubstituted Purines as Potent CDK Inhibitors Alleviating Trastuzumab-Resistance of HER2-Positive Breast Cancers

HER2-positive (HER2+) breast cancer is defined by HER2 oncogene amplification on chromosome 17q12 and accounts for 15-20% population of breast-cancer patients. Therapeutic anti-HER2 antibody such as trastuzumab is used as the first-line therapy for HER2-positive breast cancers. However, more than 50% of the patients respond poorly to trastuzumab, illustrating that novel therapy is warranted to overcome the resistance. We previously reported that in the majority of HER2+ breast-cancer patients,...