Available drugs, major drug targets, and effect profiles
| Drug . | Major drug targets . | Growth-inhibitory effects on neoplastic MCs expressing KIT D816V* . |
|---|---|---|
| Imatinib | KIT WT, KIT K509I, KIT F522C, KIT V560G, FIP1L1-PDGFRA/B | KIT D816V confers resistance to imatinib |
| Masitinib | KIT WT, LYN, PDGFRA/B | KIT D816V confers resistance to masitinib |
| Nilotinib | KIT WT, KIT D816V, KIT F522C, KIT V560G, KIT K509I, PDGFRA/B | KIT D816V confers partial resistance against nilotinib; however, some effects were seen in a pilot trial in SM patients |
| Dasatinib | KIT WT, KIT D816V, KIT F522C, KIT V560G, KIT K509I, PDGFRA/B, BTK, LYN | Growth-inhibitory effects are seen in most in vitro cell systems; however, because of the short half-life of the drug in vivo, no major durable effects were seen in SM patients |
| Midostaurin (PKC412) | KIT WT, KIT 509I, KIT F522C, KIT V560G, KIT D816V, FES, FLT3, PDGFRA/B, SYK | Growth-inhibitory effects are seen in most cell systems and in most patients with advanced SM; in addition, midostaurin blocks IgE-dependent histamine release† |
| Cladribine (2CdA) | Nucleoside metabolism | Growth-inhibitory effects are seen in most cell systems and in a subset of patients with advanced SM |
| IFN-α | Unknown‡ | Only transient and slight effects were seen in most patients with SM |
| Drug . | Major drug targets . | Growth-inhibitory effects on neoplastic MCs expressing KIT D816V* . |
|---|---|---|
| Imatinib | KIT WT, KIT K509I, KIT F522C, KIT V560G, FIP1L1-PDGFRA/B | KIT D816V confers resistance to imatinib |
| Masitinib | KIT WT, LYN, PDGFRA/B | KIT D816V confers resistance to masitinib |
| Nilotinib | KIT WT, KIT D816V, KIT F522C, KIT V560G, KIT K509I, PDGFRA/B | KIT D816V confers partial resistance against nilotinib; however, some effects were seen in a pilot trial in SM patients |
| Dasatinib | KIT WT, KIT D816V, KIT F522C, KIT V560G, KIT K509I, PDGFRA/B, BTK, LYN | Growth-inhibitory effects are seen in most in vitro cell systems; however, because of the short half-life of the drug in vivo, no major durable effects were seen in SM patients |
| Midostaurin (PKC412) | KIT WT, KIT 509I, KIT F522C, KIT V560G, KIT D816V, FES, FLT3, PDGFRA/B, SYK | Growth-inhibitory effects are seen in most cell systems and in most patients with advanced SM; in addition, midostaurin blocks IgE-dependent histamine release† |
| Cladribine (2CdA) | Nucleoside metabolism | Growth-inhibitory effects are seen in most cell systems and in a subset of patients with advanced SM |
| IFN-α | Unknown‡ | Only transient and slight effects were seen in most patients with SM |
PDGFRA/B, platelet-derived growth factor receptor α/β.
The KIT D816V mutant is detected in a majority of patients with advanced SM. However, in a few patients with MCL or other rare forms of advanced SM, other targets are detectable and may respond to imatinib and masitinib.
Midostaurin produces clinically meaningful (major) responses in about 60% of all patients with advanced SM, including a subset of patients with MCL.
IFN-α may exert growth-inhibitory effects on MC progenitor cells.