In the Cell State Targeting Unit, we tackle a crucial challenge in cancer treatment: understanding how cancer cells evolve to resist therapies and cause relapse. While the design of “personalized therapies” focuses on genetic mutations, we recognize the pivotal role of epigenetic reprogramming as a common driver of relapse in most, if not all, cancer patients. Cancer cells possess an impressive ability to adapt and survive treatment - they can evade therapies not only through genetic mutations but also via sneaky, epigenetic, mechanisms. In addition to primary resistance, where certain cells are naturally resistant to treatment, others constantly change their behavior to evade drugs (adaptive resistance). In our unit, we dive deeper into this less understood realm of epigenetic mechanisms driving malignancy. Through a multidisciplinary approach integrating high-throughput genomics, phenotypic reporters, and organoid models, we seek to explore the diverse behaviors of cancer cells. Our objective is to uncover the full spectrum of cell states present in tumors and understand how they evolve during disease progression and in response to treatments (phenotypic plasticity). Our mission to identify these resilient cell populations and unravel the molecular mechanisms behind their adaptability. By understanding how cancer cells transition between different states, we aim to design more effective therapeutic strategies that can outsmart cancer's tricks and provide long-lasting benefits for patients. Our ultimate goal is to offer hope to patients by extending their lives without the fear of cancer recurrence. By targeting the root causes of therapy resistance, we aspire to pave the way for a future where cancer treatments are not just more powerful but also durable, offering lasting relief to those affected by this devastating disease.