The introduction of ADCs into frontline ovarian cancer treatment creates a new challenge: conflicting biomarkers. A patient's tumor might be positive for both HER2 (an ADC target) and a BRCA mutation (a PARP inhibitor target), forcing clinicians to choose between two effective targeted therapies without clear guidance.

As multiple new drugs like antibody-drug conjugates (ADCs) become available for SCLC, the critical research question will shift from *if* they work to *when* they should be used. Future biomarker strategies must focus on optimizing treatment sequences, considering factors like the drug's target and payload.

Unlike early ADCs requiring high biomarker expression (e.g., mirvetuximab), next-generation agents show efficacy even in low-expressing tumors. This allows for broader, "all-comer" clinical trial inclusion criteria instead of biomarker-gated entry, potentially expanding patient access to these novel therapies.

When sequencing antibody-drug conjugates (ADCs) for SCLC, resistance may be driven more by the cytotoxic payload (e.g., a topoisomerase 1 inhibitor) than the antibody's target antigen. This suggests prior exposure to a similar payload class could predict non-response, even when using an ADC with a different target.

Experts question if HER2 status truly predicts ADC efficacy in urothelial cancer. The benefit seen across low-expression levels suggests HER2's main role may be simply to target the chemo payload to cancer cells, rather than indicating a specific biological dependency.

Emerging data shows that a second ADC, particularly one with the same payload, often has limited efficacy. This suggests clinicians must be highly strategic in selecting the first ADC, as it may be their most impactful opportunity for this class of drugs.

Contrary to expectations, TROP2 expression is not a reliable predictive biomarker for response to TROP2-targeting antibody-drug conjugates (ADCs). These drugs have shown activity across various expression levels, challenging the standard biomarker-driven approach to patient selection.

As multiple effective Antibody-Drug Conjugates (ADCs) become available, the primary clinical challenge is no longer *if* they work, but *how* to use them best. Key unanswered questions involve optimal sequencing, dosing for treatment versus maintenance, and overall length of therapy, mirroring issues already seen in breast cancer.

Despite being "targeted therapies," multiple promising antibody-drug conjugates (ADCs) for small cell lung cancer (SCLC) show no correlation between the target protein's expression level and patient response. This suggests the payload or other factors are the primary drivers of efficacy, complicating biomarker development for patient selection.