Targeting IGF signaling
IGF signaling is driven by the presence
of the ligands (IGF-1/2)
Implicated in the development and
progression of cancers
IGF signaling is
not a classic
oncogenic
‘driver’ like mutated BRAF or EGFR
Key role for IGF signaling as a
survival
response that can act as a
resistance
mechanism to limit the activity of targeted or cytotoxic agents
Thus, need for
combination
therapies with
mechanistic rationale
required
Evidence for existing IGF signaling in tumors (or potential for IGF signaling)
through analysis of elevated endocrine, paracrine, or autocrine IGF ligands, IGF-1R
phosphorylation, lack of downstream pathway mutations etc.
Optimal combination potential requires a very
good safety profile
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