Biomarker Dynamics Matter
Interventional oncologist Jason Williams warned that tumor biomarkers (KRAS, p53, MMR, etc.) change by tumor site, timing, and immune context—so a single biopsy snapshot can miss actionable biology. He framed this as a core challenge for molecular cytology and NGS sampling strategies. (x.com)
Jason R. Williams, the interventional oncologist who developed the “AblationVax” approach, has expanded on the tweet’s point in a March 2, 2026 Williams Cancer Institute essay titled “Tumor Biomarkers: Guiding Precision Immunotherapy,” where he argues that integrated genetic, metabolic and immunologic models are required to interpret biomarker signals. Contemporary reviews explicitly frame tissue biopsy as a “snapshot” that can miss spatial and temporal intratumoral heterogeneity, warning that that limitation can impair accurate treatment selection and detection of resistance mechanisms. Liquid biopsy approaches capture serial dynamics across multiple analytes—ctDNA, circulating tumor cells and exosomes—and a recent Cell Reports Medicine review details mining genomic, epigenomic, fragmentomic and transcriptomic layers from blood to track evolving actionable alterations. Analytical performance data support NGS from biofluids as a practical complement to tissue: an evaluation of a 523-gene circulating tumor DNA panel reported feasibility for comprehensive tumor profiling when tissue is limited. Large-scale spatial immune profiling found conserved tumor–immune microenvironment patterns after analyzing 2,019 tumors across 14 cancer types, demonstrating that immune contexture varies by tumor site and likely changes biomarker interpretability across lesions. Clinical guidance increasingly embeds comprehensive genomic testing into workflows: NCCN and specialty guideline updates recommend tumor gene or broad NGS profiling for advanced pancreatic cancer and updated NSCLC guidance emphasizes broad molecular testing before treatment decisions.
