Rectifying cancer drug discovery through network pharmacology
Asfar S Azmi1, Ramzi M Mohammad
1Department of Pathology, Wayne State University, 4100 John R, HWCRC 732, Detroit MI 48201, USA. azmia@karmanos.org.
Abstract:
In spite of the expensive preclinical testing, the consistent failure to translate many promising targeted drugs from the laboratory bench to the clinic raises the question of whether the single-pathway drug-discovery strategies offer the correct perspective. As revealed by network biology, cancers harbor robust biological networks that are inherently resistant to changes, such as those induced by drugs with very narrow mechanisms of action. Therefore, network pharmacology strategies, the treatment of cancer by modulating more than one target, are needed. Different promiscuous approaches targeting multiple avenues within cancer-associated networks, such as the pleiotropic natural products, are emerging. Nevertheless, there is a long way before such 'proof-of-concept strategies' can be successfully applied in the clinical setting. This article provides a perspective on the current challenges in drug discovery, the reasons for high failure rates and how network pharmacology can aid the successful design of agents against cancer.
Insights
Single-pathway drug discovery fails to translate cancer therapies to clinics. Network pharmacology, targeting multiple pathways, offers a promising strategy for developing effective cancer treatments by overcoming drug resistance.
Area of Science:
- Oncology
- Pharmacology
- Systems Biology
Background:
- Expensive preclinical testing frequently fails to yield successful clinical cancer drugs.
- Cancer's complex biological networks exhibit inherent resistance to single-target drugs.
- Current drug discovery models struggle with the multifaceted nature of cancer.
Purpose of the Study:
- To analyze the limitations of traditional drug discovery strategies in oncology.
- To highlight the potential of network pharmacology in cancer treatment.
- To discuss challenges and future directions for designing anti-cancer agents.
Main Methods:
- Review of network biology principles in cancer.
- Analysis of single-pathway versus multi-target drug strategies.
- Exploration of promiscuous drug approaches, including natural products.
Main Results:
- Single-pathway approaches are insufficient due to cancer's robust network resistance.
- Network pharmacology offers a paradigm shift by targeting multiple nodes in cancer networks.
- Pleiotropic natural products represent a promising avenue for multi-target drug design.
Conclusions:
- Traditional drug discovery faces high failure rates in translating cancer therapies.
- Network pharmacology is essential for developing more effective anti-cancer agents.
- Further research is needed to translate network pharmacology strategies into clinical practice.
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