Table 1.
Investigational therapeutic targets in lymphoma treatment
| Pathway/Protein | Oncogenic Mechanism | Molecular Target(s) | Drug Class | Investigational Drugs in Clinical Trials |
|---|---|---|---|---|
| Ubiquitin-proteasome pathway [6,7] | Dysregulation of intracellular cell cycle proteins | NF-κB inhibitory protein (IκB) | Small-molecule proteasome inhibitors | Bortezomib (PS-341, Velcade™) |
| Akt/mTOR pathway [8-10] | Aberrant activation of mTOR-mediated regulation of cell growth, proliferation, apoptosis, angiogenesis, nutrient uptake | mTORC1 (mTORC2?) | mTOR inhibitors | Temsirolimus (CCI-779, Torisel®) Everolimus (RAD001, Afinitor®) Ridaforolimus (formerly deforolimus, AP23573) |
| Cell-mediated immunity, cytokines [11] | Aberrant activation of prosurvival cytokines and cellular immune response | TNF-α, IL-6, IL-8, and VEGF; T cells and NK cells | Immunomodulatory drugs (IMiDs) | Lenalidomide (Revlimid®) |
| VEGF receptors, PDGF receptors [12,13] | Tumor proliferation, angiogenesis | Tyrosine kinase | Tyrosine kinase inhibitors | Sunitinib (SU11248, Sutent®) Sorafenib (Nexavar®) |
| Histone deacetylase [14] | Dysregulated histone deacetylation in promoters of growth regulatory genes (gene silencing) | Histone deacetylase | Histone deacetylase inhibitors (HDACIs) | Vorinostat (Zolinza®) Romidepsin (FK228) Valproic acid Panobinostat (LBH589) Others |
Abbreviations: IL-6 = interleukin-6; IL-8 = interleukin-8; mTOR = mammalian target of rapamycin; PDGF = platelet-derived growth factor; PI3K = phosphoinositide 3-kinase; TNF-α = tumor necrosis factor-alpha; VEGF = vascular endothelial growth factor.