Secondary Mutations cause Resistance to Gleevec

1
Secondary Mutations cause Resistance to Gleevec

• The Life Raft Group
• February 2006

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2
Failure to Inhibit KIT-secondary mutations

• Possible Solutions
• Different KIT inhibitor with activity against
  both the primary and secondary mutation.
  Possibilities include
• Sutent (approved in US)
• AMG706
• BMS-354825
• BAY 43-9006
• Destroy KIT protein
• IPI-504
• Combinations Gleevec
• AMN107, PKC412, etc

Prior to treatment with Gleevec none of 112 GIST
samples had more than one activating mutation in
KIT or PDGFRA (Heinrich MC, et al. J Clin Oncol
2003. 214342-49)
Common initial mutations