Drug combinations targeting the two signaling pathways (Cyclin D/CDK/Cdkn2a/Rb and PI3K/AKT/Mtor) identified by our genetic analysis of PCT susceptibility, were indeed synergistic in their activity, not only for myeloma, but also a variety of tumor types as shown in their broad synergistic activity in the panel of NCI-60 cell lines. Here, AKT1 is linked to plasma cell myeloma.