Cancer Diagnostics Haven't Kept Up with ADC Science

A 2026 review urges quantitative proteomics to replace IHC and improve patient selection for ADC cancer therapies

30 Mar 2026

A review published in Clinical Cancer Research in February 2026 is calling for a fundamental change in how cancer patients are selected for antibody-drug conjugate therapies, arguing that current diagnostic practice has failed to keep pace with treatment advances.

ADCs have become one of oncology's most active development areas. The FDA has approved 15 such therapies across multiple tumour types, with more in late-stage trials. The central problem, the review argues, is that identifying which patients will respond remains unreliable.

The paper, led by McNamee and colleagues, centres its critique on immunohistochemistry, the standard method for assessing whether a tumour expresses the protein an ADC is designed to target. IHC measures one or two proteins at a time through visual scoring and captures only a single biopsy site at a fixed moment. It cannot track how antigen levels differ across tumour sites or shift during treatment, both of which bear directly on whether a therapy will work.

The proposed replacement is quantitative mass spectrometry-based proteomics, a technology capable of measuring hundreds of proteins simultaneously with numerical precision. The authors argue for integrating multiplexed proteomic assays into early-phase clinical trial design, with the aim of improving patient matching, raising response rates, and limiting exposure to treatments unlikely to benefit individual patients.

The case for change has sharpened as ADCs multiply and compete within the same indications. Clinicians are increasingly being asked to choose between therapies without the biomarker data to do so with confidence.

Proteomic validation and workflow integration will require time and investment. The authors present these as realistic near-term goals rather than distant ambitions, though the path from research proposal to routine clinical use involves regulatory, logistical, and cost hurdles that the review does not fully address. Whether trial sponsors and health systems will commit the resources needed to shift diagnostic infrastructure remains an open question.