The re-BOOT consortium is a transnational, interdisciplinary initiative dedicated to overcoming drug resistance in aggressive B-cell cancers. Building upon the research foundations of the BATMAN and HiRisk-HiGain projects (funded by ERA PerMed and EP PerMed), the consortium focuses on a specific “master switch” that allows cancer cells to evade treatment: the BOB1-OCT2 complex. In malignant cells, this molecular switch reorganises the 3D structure of chromatin, creating a “pro-cancer” environment that fuels tumour progression and resistance. To combat this, re-BOOT is developing first-in-class small-molecule inhibitors designed to dismantle these harmful structures and “rewire” malignant cells back to a non-oncogenic state. By leveraging cutting-edge biophysics -such as optical tweezers integrated with super-resolution microscopy – the consortium aims to visualise the mechanisms of action of these novel inhibitors in real-time. A central focus of the re-BOOT networking event in Nantes, France (September 2026), is to engage key stakeholders, including experts in oncology, biophysics, the Carnot Institute CALYM, and its partners including the patient advocacy organisation ELLyE. Together, these partners will work to identify molecular signatures and companion biomarkers essential for accurate patient stratification. This ensures that high-risk patients receive tailored, effective therapies. Ultimately, the re-BOOT networking event aims to establish a strategic roadmap for the transition to clinical trials. By uniting experts across diverse fields, the consortium aims to provide a lifeline for patients with currently incurable lymphoid malignancies, transforming high-risk cancer treatment through the power of precision medicine.