Important fundamental breakthroughs in cancer biology have come from the basic research discovery that defects in the tumor suppressor and DNA repair genes BRCA1/2 genes predispose to breast, ovarian, prostate, and pancreatic cancers. Furthermore, the game-changing synthetic lethality concept for defects with inhibitors to Poly-ADP-Ribose Polymerase 1 (PARP1) is transforming clinical cancer therapy and prompting many new clinical trials. Yet, key gaps in our molecular and mechanistic understanding of therapy efficacy limit our ability to fully harness the insights from DNA damage responses gained so far. In this context, striking ongoing advances in methods and results spanning from molecules to cells and organisms are implicating functionally-important molecular communications coupling the DNA damage response, responses to DNA replication fork instability and DNA-based immune response. Future master keys to cancer biology and advanced therapies will benefit from better defining these distinct cellular stress responses, their mechanistic interconnectivity, and their implications for cancer biology and therapeutic outcomes. The 6th DNA Repair/Replication Structures & Cancer conference on 14-18 February 2024 will focus on molecular structural and mechanistic insights into dynamic complexes acting in DNA repair, replication, and inflammation and their intersections relevant to advanced cancer therapies. This fundamental information will be pivotal for pioneering research on DNA damage responses as well as for the accurate interpretation of cancer clinical data, design of clinical trials, prognosis, etiology and improving the currently low success rate for oncology drug clinical trials. Informative talks and poster sessions along with vibrant discussions will foster productive interactions, collaborations, and insights. In this conference and this area of science basic research is empowering medical advances and clinical data are unveiling basic relationships in ways that are completely changing how research and translation is being done.