For the millions of women with metastatic breast cancer, knowing whether a targeted therapy is actually reaching and killing tumor cells — in real time, without repeated biopsies — has been an unsolved clinical problem. A new approach using circulating tumor cells (CTCs) as liquid biopsy surrogates may change how oncologists assess and adapt antibody-drug conjugate (ADC) treatments, potentially preventing weeks of ineffective therapy.
The research, published in PNAS, focused on two ADCs now central to breast cancer treatment: one targeting TROP2 and one targeting HER2. By isolating CTCs from patient blood samples, investigators were able to dynamically measure surface expression of TROP2 and HER2 on individual cancer cells, as well as monitor intracellular payload delivery — the actual drug release that determines whether an ADC is pharmacologically active. This dual read-out, tracking both antibody docking and cytotoxic cargo release, offered a more complete mechanistic picture than tissue biopsies or imaging alone. The cohort and specific effect sizes were not disclosed in the excerpt, but the approach was validated as a real-time pharmacodynamic monitoring platform.
This work sits at a clinically important intersection: ADC resistance is increasingly recognized as a major obstacle, and heterogeneous antigen expression — meaning not all tumor cells in a patient display the same target density — is a leading driver of incomplete response. Existing tissue biopsies capture a single tumor site at one moment in time, missing spatial and temporal variation. The CTC-based approach addresses both limitations by sampling shed cells from across the tumor burden and enabling serial monitoring over treatment cycles. Key limitations to note: CTC capture efficiency varies by platform, and very low CTC counts in some patients may constrain assay reliability. Whether this monitoring approach will translate into improved survival outcomes via treatment adaptation remains to be demonstrated in prospective trials. Still, as a pharmacodynamic tool, this is a meaningful and potentially practice-shaping advance in precision oncology.