Discovery and development of novel therapies in advanced breast cancer: rapid development of ribociclib

Abstract

The treatment landscape for advanced breast cancer has changed radically over the last 30–40 years with the refinement of surgical and radiographic techniques, approval of a range of chemotherapy regimens in the adjuvant and metastatic settings, and improvements in screening procedures. A deeper understanding of the molecular pathways underpinning tumor growth has led to the identification and development of a number of targeted therapies with particularly high activity in breast cancer. As an example, the prognosis of women with human epidermal growth factor receptor 2-positive (HER2+) breast cancer has improved dramatically since the introduction of HER2-targeted therapies [1]. Meanwhile, in hormone receptor-positive (HR+) breast cancer, the mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to be effective in combination with exemestane [2]. Overall, these innovations have led to the earlier detection of breast cancers and better treatments, resulting in significant improvements in patient survival and quality of life. Finding future treatments for breast cancer will depend on gaining more insights into the pathways driving tumor growth and the mechanisms of acquired and de novo resistance. Investigational targeted agents currently in clinical development include the phosphatidylinositol 3-kinase (PI3K) inhibitor alpelisib (BYL719) and the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (LEE011).