Examples of novel targeted approaches for the treatment of mantle cell lymphoma (MCL).
| Mechanism . | Drugs . | Rationale . |
|---|---|---|
| Inhibition of antiapoptotic Bcl-2 family members | ABT-737/263 AT-101 GX015- oblimersen | Silence the antiapototic influence of Bcl-2, Bcl-xl, Bcl-w and Mcl-1 |
| Modulation of proapoptotic family members and BH3-only proteins | Proteasome inhibitors (bortezomib, PR-171) | Up-regulation derepression of proapoptotoic family members will lead to induction of programmed cell death |
| Down-regulation of cyclin D1 and related isofroms | Cyclin D1 antisense (ASDON) Histone deacetylase inhibitors (SAHA) | Down-regulation of cyclin D1 and related isoforms will decrease the driving force for cells to transition from G1 into S-phase, producing cell-cycle arrest |
| Increase cell-cycle–dependent kinase inhibitors like p27/p21 | Proteasome inhibitors HDACI | A relative increase in cdk inhibitors will provide the“breaks” on cell-cycle proliferation, inducing cell cycle arrest |
| Inhibition of pan–cell-cycle– dependent kinases | Flavopiridol AG-024322 | Induce cell-cycle arrest |
| Inhibition of selective cell-cycle– dependent kinases | PD-0332991 (cdk4/6) CINK4 (cdk4/6) Seliciclib (cdk2/1) BMS-387032 (cdk2/1) PNU-252808 (cdk2/1) PNU-252808 (cdk2/1) NU6102, NU6140 (cdk2/1) | Inhibit specific phase transitions of cell-cycle progression |
| Inhibit protein translation and signaling pathways mediated through tyrosine kinase receptors and ras | mTOR inhibitors (most derived from rapamycin, including temsirolimus), AKT inhibitor | Associated with a broad effect on cancer cell biology, including translation, NF-κB, transcription factors, and apoptosis |
| Mechanism . | Drugs . | Rationale . |
|---|---|---|
| Inhibition of antiapoptotic Bcl-2 family members | ABT-737/263 AT-101 GX015- oblimersen | Silence the antiapototic influence of Bcl-2, Bcl-xl, Bcl-w and Mcl-1 |
| Modulation of proapoptotic family members and BH3-only proteins | Proteasome inhibitors (bortezomib, PR-171) | Up-regulation derepression of proapoptotoic family members will lead to induction of programmed cell death |
| Down-regulation of cyclin D1 and related isofroms | Cyclin D1 antisense (ASDON) Histone deacetylase inhibitors (SAHA) | Down-regulation of cyclin D1 and related isoforms will decrease the driving force for cells to transition from G1 into S-phase, producing cell-cycle arrest |
| Increase cell-cycle–dependent kinase inhibitors like p27/p21 | Proteasome inhibitors HDACI | A relative increase in cdk inhibitors will provide the“breaks” on cell-cycle proliferation, inducing cell cycle arrest |
| Inhibition of pan–cell-cycle– dependent kinases | Flavopiridol AG-024322 | Induce cell-cycle arrest |
| Inhibition of selective cell-cycle– dependent kinases | PD-0332991 (cdk4/6) CINK4 (cdk4/6) Seliciclib (cdk2/1) BMS-387032 (cdk2/1) PNU-252808 (cdk2/1) PNU-252808 (cdk2/1) NU6102, NU6140 (cdk2/1) | Inhibit specific phase transitions of cell-cycle progression |
| Inhibit protein translation and signaling pathways mediated through tyrosine kinase receptors and ras | mTOR inhibitors (most derived from rapamycin, including temsirolimus), AKT inhibitor | Associated with a broad effect on cancer cell biology, including translation, NF-κB, transcription factors, and apoptosis |