Targeted therapy in lymphoma

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.

ISSN: 1756-8722