The landscape of targeted therapies for breast cancer is rapidly expanding, according to a recent review published in Biochemical Pharmacology.
Today, numerous classes of drugs for breast cancer exist or are under development, each with unique mechanisms of action. Because breast cancer cells exist in a complex tumor microenvironment composed of immune cells, blood vessels and many other components, researchers are exploring a wide range of pathways as potential therapeutic targets.
For example, bi-specific antibodies, which can bind to two different antigens, can alter several signaling pathways at the same time. Potential targets include human epidermal growth receptor factor 2 (HER2) and programmed death-ligand 1 (PD-L1), an immune checkpoint protein. Clinical trials investigating bi-specific antibodies are underway.
Antibody-drug conjugates are another promising option for treating breast cancer. They work by binding to proteins expressed on tumor cells and releasing a drug, such as chemotherapy, to kill the cells. “This design enables the precise administration of potent pharmaceuticals directly to neoplastic cells that exhibit specific surface antigens,” the authors explained.
Read more about breast cancer therapies
Currently, four antibody-drug conjugates are approved in the United States to treat breast cancer: trastuzumab emtansine, trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan. Trastuzumab deruxtecan has a emerged as a particularly potent option in HER2-positive settings. In triple negative breast cancer, sacituzumab govitecan is a standard of care. However, the cost of these medications remains very high.
Furthermore, poly ADP-ribose polymerase (PARP) inhibitors are an established group of drug that damage tumor cell DNA, causing cell death. Olaparib was the first PARP inhibitor to be approved by the US Food and Drug Administration, receiving approval in 2014. Since then, researchers have developed PARP inhibitors for various cancers.
Other therapies targeting elements of the tumor microenvironment include cyclin-dependent kinase (CDK) 4/6 inhibitors, which halt the cell cycle, fibroblast growth factor receptor inhibitors and immune checkpoint inhibitors. AKT inhibitors and MEK inhibitors block molecular pathways that play a role in cancer development and cell growth. Anti-angiogenic drugs are yet another class of medicine that cut off blood supply from tumors.
The authors also discuss the potential of breast cancer vaccines. These go beyond the tumor microenvironment to induce an immune response against cancer cells. Vaccines may target proteins such as HER2, MUC1 or α-lactalbumin, which can all be expressed on the tumor cells.
With any of these novel therapies, though, comes the risk of drug resistance over time. Therefore, efforts are ongoing to overcome mechanisms of drug resistance and explore potential combination therapies.
“The remarkable expansion of targeted and immunological strategies in breast cancer has fundamentally transformed patient outcomes, yet this progress illuminates an increasingly complex therapeutic landscape,” the authors concluded. “The challenges are substantial, but the foundation laid by the past decade of discovery provides unprecedented opportunity to transform breast cancer from a life-threatening disease to a chronically managed condition for patients worldwide.”
Sign up here to get the latest news, perspectives, and information about breast cancer sent directly to your inbox. Registration is free and only takes a minute.