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Targeting IAP proteins for therapeutic intervention in cancer

Simone Fulda1, Domagoj Vucic

  • 1Institute for Experimental Cancer Research in Pediatrics, Goethe University Frankfurt, Komturstr. 3a, 60528 Frankfurt, Germany. simone.fulda@kgu.de

Nature Reviews. Drug Discovery
|February 2, 2012
PubMed

Insights

Cancer cells evade apoptosis using inhibitor of apoptosis (IAP) proteins. Targeting IAP proteins, particularly through SMAC-mimicking drugs, offers a promising therapeutic strategy for human malignancies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Evasion of apoptosis is a hallmark of cancer, enabling resistance to therapy.
  • Inhibitor of apoptosis (IAP) proteins are key regulators of cell death, promoting cancer cell survival and proliferation.
  • Dysregulation of IAP genes (mutations, amplifications, translocations) is linked to various cancers.

Purpose of the Study:

  • To provide an updated review of Inhibitor of Apoptosis (IAP) protein biology.
  • To discuss current and future therapeutic strategies targeting IAP proteins in human malignancies.

Main Methods:

  • Review of existing literature on IAP protein function and therapeutic targeting.
  • Analysis of IAP-binding motif of second mitochondria-derived activator of caspase (SMAC) as an antagonist.
  • Exploration of alternative strategies like transcriptional repression and antisense oligonucleotides.

Main Results:

  • IAP proteins, including XIAP and cellular IAPs, play critical roles in inhibiting apoptosis through direct caspase inhibition or blocking pro-apoptotic signaling.
  • SMAC-mimicking drugs represent a primary therapeutic approach by antagonizing IAP function.
  • IAP dysregulation is a significant factor in cancer development and progression.

Conclusions:

  • Targeting IAP proteins is a viable therapeutic strategy for treating human cancers.
  • SMAC-mimetic drugs and other novel approaches hold significant promise for overcoming apoptosis evasion in cancer therapy.
  • Further research into IAP biology and therapeutic interventions is crucial for advancing cancer treatment.

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