Topic: Circulating Biomarkers and Minimal Residual Disease (MRD) in Cancer Therapy Resistance

Minimal residual disease (MRD) consists of drug-resistant tumor cells that persist following treatment and drive therapeutic resistance, and represents a major challenge in cancer management. MRD is presented dynamically as persister/dormant/quiescent/drug-resistant cancer cells in residual tumors and may also be detected as circulating tumor cells (CTCs) in peripheral blood or as disseminated tumor cells in the bone marrow and other metastatic niches where resistance emerges. The biological behavior, survival, acquisition of drug resistance, and therapeutic response of these residual cancer cells are profoundly influenced by their surrounding microenvironment, including cytokines, hormones, stromal and immune cell interactions, epigenetic reprogramming, and exposure to anticancer therapies that select for resistant phenotypes.

This focus is particularly timely: multiple prospective interventional trials evaluating MRD-guided treatment strategies are reporting results in 2025–2027 (e.g., DARE-2, c-TRACK CRC, RAILWAY), revealing that MRD represents not merely residual disease but a functional reservoir of drug-resistant clones that seed clinical relapse. This Special Topic aims to capture this wave by welcoming submissions that present early trial data, secondary analyses, and methodological innovations for tracking and targeting drug-resistant clones in the MRD setting.

The aim of this Special Topic is to provide a comprehensive overview of current advances in the characterization and clinical exploitation of minimal residual disease as a dynamic interface between cancer biology and therapeutic resistance. In particular, it will focus on: (i) the technological challenges associated with CTC detection for capturing drug-resistant clones, including a critical description of currently available methodologies and an overview of the most recent innovative approaches supported by emerging clinical evidence to predict treatment failure; (ii) the clinical applications and potential utility of CTC detection in a series of rare cancers, where biomarkers for resistance and relaps remain limited and unmet clinical needs are substantial for precision salvage therapy; and (iii) the monitoring of antitumor immune responses, with a particular emphasis on T-cell exhaustion as a biomarker of therapeutic resistance, and resistant clone immune evasion, as well as the development of strategies and drugs aimed at enhancing immune recognition and elimination of drug-resistant residual cancer cells.

Topics of interest include, but are not limited to:

● MRD Technologies for Capturing Drug-Resistant Clones;

● MRD as a Readout of Therapy Resistance;

● MRD-Guided Treatment Adaptation and Resistance Overcoming;

● Multi-Modal Liquid Biopsy for Resistance Monitoring;

● Immune Evasion and T-Cell Exhaustion in MRD.

● etc.