Together, multi-targeted combinatorial personalized precision therapies composed of multiple novel agents highly selectively targeting at distinct cellular pathways and DLBCL subtypes (i.e., ABC, GCB) or subsets (i.e., BCR, OxPhos, MD or HR) combined with ADC or conventional rituximab based chemotherapy will most likely represent the future mainstay of treatment for patients with newly diagnosed high-risk DLBCL or relapsed/refractory DLBCL and thus may provide hope for relapsed patients who have failed current chemotherapies in the rituximab era. The gene discussed is BCR; the disease is diffuse large B-cell lymphoma.