Table 1 B cell pathways frequently disrupted and therapeutic agents that inhibit key pathway molecules.

Major B cell signaling pathways and its common mode of disruptions are shown. Within each pathway, key molecules or processes can be inhibited by various therapeutic agents, either FDA-approved or under development.

Up-regulated
pathways
Mode of
disruption
Possible
therapeutic
agents
Current
settings
BCR pathwaySomatic
mutation
BTK inhibitors:
ibrutinib and
acalabrutinib
Ibrutinib:
FDA-approved
Acalabrutinib:
FDA-approved
(NCT02029443)
NF-κВ pathwaySomatic
mutation
Angiogenesis
inhibitor:
lenalidomide
Proteasome
inhibitor:
velcade
(bortezomib)
Lenalidomide:
under FDA
review
Bortezomib:
FDA-approved
Cell cycle controlSomatic
mutation;
epigenetic
suppression
CDK4/CDK6
inhibitor:
abemaciclib
Phase 3
(FDA-approved
for breast
cancer)
Apoptosis/p53
pathway
Somatic
mutation
Bcl-2 inhibitor:
venetoclax
AKT/ERK
inhibitor:
ONC201
MDM2
inhibitors
Venetoclax:
phase 2
DNA damage repair
pathway
Somatic
mutation:
epigenetic
suppression
Poly
ADP-ribose
polymerase
inhibitor:
olaparib
Phase 1
PI3K pathwaySomatic
mutation
PI3K inhibitors:
idelalisib,
KA-2237, and
TGR-1202
Idelalisib: phase 1
Oxidative
phosphorylation
(OXPHOS)
pathway
Metabolic
disruption
Mitochondrial
complex I
inhibitor:
IACS-010759
Phase 1