Based on all the data we collected in HB cells, PDXs and primary patient tumors, we propose a dynamic RNR M2 subunit switching model in supporting HB cell proliferation versus survival—RRM2 is the dominant RNR M2 subunit supporting HB cell growth; RRM2 switches to RRM2B when drug treatment inhibits cell proliferation and induces stress; once helping cells survive the stress, RRM2B switches back to RRM2 for its better ability to support tumor cell regrowth (Fig. 8c). Here, RRM2B is linked to neoplasm.