Antibody–drug conjugates (ADCs)

What it is

An antibody–drug conjugate has three parts: a monoclonal antibody that recognizes a specific protein on cancer cells, a powerful cytotoxic “payload,” and a chemical linker joining them. The antibody delivers the toxic drug straight to cells carrying the target, so a very potent chemotherapy can be used with less exposure to healthy tissue. ADCs have changed treatment of HER2-positive and HER2-low breast cancer (trastuzumab deruxtecan), triple-negative breast and urothelial cancers (sacituzumab govitecan, enfortumab vedotin), certain lymphomas (brentuximab vedotin) and others. They blur the line between targeted therapy and chemotherapy.

Why it's done

• Cancers expressing the ADC’s target protein (e.g., HER2, Trop-2, Nectin-4, CD30)
• HER2-positive and HER2-low breast cancer; triple-negative breast cancer
• Urothelial (bladder) cancer, some lymphomas, and a growing list of others
• Often after, or instead of, standard chemotherapy

How it’s given

By IV infusion on a repeating schedule, in an outpatient setting. Eligibility depends on testing the tumor for the relevant target protein.

What to expect

Given in cycles like chemotherapy, with monitoring of blood counts and organ function. Side-effect profiles are specific to each ADC’s payload and target.

Risks & side effects

• Low blood counts, nausea, hair loss and fatigue (from the chemo payload)
• Drug-specific effects — e.g., lung inflammation (interstitial lung disease) with some ADCs, neuropathy or skin/eye effects with others
• Infusion reactions
• Requires the target protein to be present on the cancer

Alternatives