Targeted therapy by disabling crossroad signaling networks: the survivin paradigm

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Targeted cancer therapy aims to disable specific oncogenic pathways, but faces challenges like multiple genetic lesions and drug resistance.
• Identifying a single driving oncogenic pathway is difficult in many tumors, limiting the efficacy of traditional targeted approaches.
• Cancer stem cell compartments can be insensitive to therapies targeting single pathways.

Purpose of the Study:

• To explore targeting crossroad signaling networks as a broader therapeutic strategy in cancer.
• To investigate survivin as a central target within these networks.
• To evaluate the potential of survivin-targeting therapies in overcoming limitations of single-pathway inhibition.

Main Methods:

• Review of current understanding of targeted cancer therapy limitations.
• Analysis of survivin's role in intersecting cell proliferation, survival, and stress response pathways.
• Overview of ongoing clinical trials investigating survivin-targeting agents (immunotherapy, small-molecule antagonists).

Main Results:

• Survivin integrates multiple critical cancer cell functions, making it a key crossroad target.
• Targeting survivin can simultaneously disable multiple signaling circuitries exploited by cancer cells.
• Multiple therapeutic approaches targeting survivin are in clinical development.

Conclusions:

• Targeting survivin presents a novel perspective for rational cancer therapy.
• This approach may be broadly applicable to various tumor types, irrespective of their genetic makeup.
• Simultaneously disabling multiple pathways via survivin may overcome drug resistance and target cancer stem cells.