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Editorial: The insights of multi-omics into the microenvironment after tumor metastasis: a paradigm shift in molecular targeting modeling and immunotherapy for advanced cancer patients, volume II

Year: 2026

Type: editorial

Abstract: new targeted drugs and immune checkpoint blockers(3), many patients with advanced disease do not achieve long-term remission (4). The tumor microenvironment after metastasis is an active ecosystem where cancer cells constantly change their surroundings to grow, evade immunity, and resist treatment (3). Traditional bulk-omics average signals across many cell types, masking rare but clinically decisive subclones (5). The second volume of our Research Topic addresses this gap through single-cell transcriptomics, spatial profiling, proteomics, epigenomics, radiomics, and functional validation. The 15 articles collected here converge on a central tenet: effective therapy for advanced cancer must target both the seed and the soil, and multi-omics provides the roadmap.Several studies identify molecular hubs operating at the tumor-stroma interface. Despite these advances, we must acknowledge the limitations that still pervade the field. First, much of the mechanistic evidence remains correlative or derived from preclinical models. Large-scale prospective validation in independent patient cohorts is scarce. The functional context-dependence of many regulators means that a one-size-fits-all therapeutic approach is unlikely to succeed. For example, SERPINE2 may act differently in lung versus liver metastases. PTPRR's role may vary by KRAS mutation status. Second, the development of specific, clinically druggable inhibitors for these targets is still in its infancy. For extracellular targets like SERPINE2 and PTPRR, neutralizing antibodies or ligand-traps are conceptually feasible. But their pharmacokinetics, tissue penetration, and on-target toxicity in normal stroma remain unknown. Third, the spatiotemporal heterogeneity of metastatic lesions demands not only static biomarkers but also dynamic monitoring tools. Radiomics and liquid biopsies could play a pivotal role here. Fourth, while the FAPI imaging study by Zhou et al. is a pioneering effort, the small sample size (n=17) and the lack of immunohistochemical validation of FAP expression mean that the findings should be interpreted as hypothesis-generating rather than definitive. Fifth, for the GAA study in AITL, the relatively small sample size and the correlative nature of the analyses preclude definitive conclusions regarding causality; functional studies manipulating GAA expression will be required to clarify its mechanistic role. Sixth, the CD8 + T cell dynamics model by Xie and colleagues requires external validation in multicenter prospective cohorts, and its applicability to emerging immunotherapy scenarios such as neoadjuvant therapy or adjuvant treatment without measurable lesions remains to be established.Looking ahead, we see three priorities. First, rigorous clinical validation of multi-omics-derived signatures in multicenter, prospective trials is essential (6)(7)(8).Second, integrating spatial omics with longitudinal imaging will allow us to track TME evolution during therapy and adapt regimens accordingly. This approach aligns with the emerging concept of adaptive precision oncology (9). Third, artificial intelligence-driven multi-omics integration should move beyond cluster discovery to generate actionable predictive models that can be deployed at the bedside (4,6). We are convinced that the insights gathered in this Research Topic will catalyze a fundamental reorientation: from treating cancer as a genetic disease to manage it as an ecosystem disorder. This shift promises to improve outcomes for patients with advanced malignancies.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1986038