Transformando la práctica clínica del paciente con Cáncer de Pulmón ALK positivo

4 / 53

Activation of ALK triggers pathways involved in proliferation and
cell survival in normal physiology
Dimerisation
promotes ALK
autophosphorylation2
3
Phosphate
group
P P
Binding of the
ligands (the growth factors
MK or PTN) to ALK
induces dimerisation2
2
MK or
PTN
Inside
Outside
Cell
membrane
ALK is a membrane-
bound protein1
1
Activation
of signalling
pathways
MAPK STAT3 PI3K/
AKT
Proliferation Cell survival
Ligand-dependent activation
of downstream intracellular
signalling pathways1,2
4
P P
Inside
EML4-ALK activates signalling cascades in the
absence of ligand binding which promotes tumour growth
Activation
of signalling
pathways
MAPK STAT3 PI3K/
AKT
EML4-ALK is
localised within
the cytoplasm1
Independently of
ligand binding, EML4
mediates dimerisation
of EML4-ALK2
EML4-ALK dimerisation
promotes EML4-ALK
autophosphorylation2
1 3 2
EML4-ALK promotes tumour-cell growth and survival through the aberrant activation of pathways involved in
Proliferation Cell survival
P P
P
P
In the absence of ligand binding,
EML4-ALK is constitutively active
and activates intracellular
signalling cascades1,2
4