Diffuse Large B-cell lymphoma (DLBCL), a cancer arising from B-lymphocytes (a subtype of white blood cells), is currently treated by immuno-chemotherapy, which cures about 60% of the patients, while others eventually relapse. Resistance to therapy results from cancer-associated mutations that are variable from patient to patient – utilizing those features to guide tailored therapeutic approaches is the essence of personalised medicine.

A particularly high-risk scenario in DLBCL is the co-activation of two cancer-promoting genes, termed MYC and BCL2, resulting in so-called “double-hit” lymphomas. We previously reported that in animal models these tumors can be eradicated by the combination of two drugs, Venetoclax and Tigecycline. Here, we will use an innovative personalised scheme to translate those findings into the clinic.

Following an initial response to standard treatment, patients will receive Venetoclax and Tigecycline to eradicate residual disease, thus averting relapse. Blood samples will be collected at each step and subjected to genomic analyses, allowing to detect even rare tumor cells and map their mutation profiles. Hence, we shall not only assess the efficacy of the drug combination in the clinic, but also decipher the molecular features that distinguish responders from non-responders, thus guiding the introduction of this new personalised therapy in routine healthcare.