Figure 2. Major aberrant pathways in MCL susceptible to targeted therapies.
Numerous signaling pathways are constitutively activated and/or deregulated in MCL, including BCR, BAFF-R, mTOR, WNT, and NOTCH1 signaling as well as pathways that promote the cell cycle and inhibit apoptosis. mTOR and proteasome inhibitors are the only two pathways for which specific drugs have been approved. Several small molecules targeting the BCR and the PI3K/AKT/mTOR pathway at different levels (indicated by white text) are currently being studied in clinical trials. Other clinical trials are using small molecules to target the BCL2 family proteins directly involved in apoptosis and the cyclin-dependent kinases (CDKs) directly involved in the progression through G1/S and G2/M phases of the cell cycle. The WNT and NOTCH1 pathways are potential targets for β-catenin (β-cat) inhibitors and NOTCH1 inhibitors, respectively. Pharmacologic inhibition of PARP activity has become an interesting therapeutic strategy in tumors with dysfunctional DNA repair mechanisms, such as MCL.