Imagine a drug that can attack only cancer cells like a guided missile, while sparing normal tissue as much as possible—this is exactly the design concept of antibody-drug conjugates (ADCs). An ADC consists of three parts: a monoclonal antibody that recognizes antigens on the surface of cancer cells, a potent cytotoxic drug (payload), and a chemical linker that connects the two. The antibody navigates, the chemotherapy drug attacks, and the linker ensures the toxin is released only after entering the cancer cell.
A Success Story in HER2-Positive Breast Cancer
The most striking achievements of ADCs in breast cancer come from HER2 targeting. In multiple phase III trials, next-generation HER2 ADCs significantly prolonged progression-free survival and overall survival compared with older-generation drugs, and have gradually moved from later-line treatment to second-line and even first-line settings. The 'bystander effect' in their drug design allows the released toxin to penetrate cell membranes and kill neighboring cancer cells that do not express HER2, which is particularly important for tumors with uneven antigen expression.
Redefining 'HER2-Low'
An even more revolutionary finding is that patients traditionally classified as HER2-negative but with immunohistochemistry staining of 1+ or 2+, known as 'HER2-low', can also benefit from HER2 ADCs. This group accounts for more than half of so-called HER2-negative breast cancer and previously could only rely on chemotherapy. Now the treatment classification has been rewritten. This reminds us: every number on a pathology report may take on new meaning with the emergence of new drugs.
Triple-Negative Breast Cancer and Future Directions
In triple-negative breast cancer, ADCs targeting Trop-2 have been proven superior to chemotherapy in later-line treatment and are rapidly advancing to earlier lines, even combined with immunotherapy for neoadjuvant treatment. The research and development directions for next-generation ADCs include bispecific antibodies, designs carrying two different toxins, and development against new targets such as HER3.
It is important to note that ADCs still have their specific side effects, such as interstitial lung disease, peripheral neuropathy, and low blood cell counts, and regular monitoring is required during treatment. Multiple clinical trials of ADCs for Taiwanese patients are currently recruiting. Patients who have not responded well to standard treatment can discuss with their attending physician whether they are suitable to participate.