Antibody-drug conjugates (ADCs) are a targeted approach to treating breast cancer. This class of drug has revolutionized the treatment landscape by acting as a “smart” chemotherapy that recognizes and distinguishes cancer cells from healthy ones.
Currently, four ADCs are approved in the United States to treat breast cancer, with several additional ADCs approved for other types of cancers.
Structure of ADCs
ADCs consist of three main components: a monoclonal antibody, a linker and a cytotoxic payload.
Antibody: ADCs contain many identical copies of a specific lab-produced antibody known as a monoclonal antibody. These antibodies are able to target and bind to proteins that exist on the surface of cancer cells. It is because of the monoclonal antibody that ADCs precisely target cancer cells and not healthy ones.
Linker: The purpose of the linker is to connect the antibody with the chemotherapy that will be unloaded into the cell.
Payload: The cytotoxic payload is a very potent form of chemotherapy that directly enters cancer cells to kill them. Unlike traditional chemotherapy, which often flows throughout the entire body, ADCs are designed to only send chemotherapy to the tumor cells. As a result, this option often uses a more powerful drug than what might be possible with systemic chemotherapy.
Learn more about breast cancer therapies
ADCs can treat multiple breast cancer types
The ADCs approved to treat breast cancer are:
- Trastuzumab emtansine (T-DM1)
- Trastuzumab deruxtecan (T-DXd)
- Sacituzumab govitecan
- Datopotamab deruxtecan (Dato-DXd)
T-DM1 and T-DXd have shown to be effective among individuals with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, including metastatic settings. Recent evidence has demonstrated that T-DXd outperforms chemotherapy in HER2-low disease as well.
Among individuals with hormone receptor-positive, HER2-negative cancer, Dato-DXd has exhibited promising findings.
In patients with triple-negative breast cancer, a subtype that is notoriously difficult to treat, sacituzumab govitecan has emerged as a standard of care.
Side effects of ADCs
Even though ADCs are created to have fewer systemic side effects than some other treatments, they are not risk-free. Some of the common adverse events associated with ADC use include:
- Diarrhea
- Vomiting and nausea
- Headaches
- Decreased appetite
- Fatigue
- Hair loss
- Low blood cell counts
Many of these side effects overlap with those of traditional chemotherapy.
In addition to these side effects, ADCs are associated with increased risk of liver and lung damage, along with severe gastrointestinal and neurologic symptoms.
Between the side effects and high cost of ADVs, their reach remains somewhat limited. Although ADCs have come a long way since their inception, there is still more to be done when it comes to managing toxicity and expanding accessibility.
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