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Molecules for the millennium: how will they look? New drug discovery year 2000
1Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 6130 Executive Blvd. Suite 8000, Rockville, MD 20852, USA.
Abstract:
A new approach to cancer drug discovery targets molecules important in cancer pathogenesis. This approach is thought to be of greater promise than the antiproliferative screens which discovered cytotoxic agents and dominated cancer drug discovery for 60 years. However, one cannot lose sight of the fact that these targets exist in the cellular environment consisting of many additional influences on target function, and that effective drug treatment will take into account drug uptake, metabolism and elimination at the level of the cell as well as the organism. A key goal is to define for the new millennium a path to cancer drug discovery and development which accounts for the cancer cell phenotype in its totality rather than as arising solely from single molecular targets. The US National Cancer Institute maintains a cell-based drug discovery screen which can define a context for drug action in the milieu of more than 300 molecular targets and thousands of gene expression patterns which have been measured in the 60 human tumour cell lines which comprise the screening panel. The challenge of the millennium will be addressed by molecules active against defined targets but with selectivity of action occurring in the milieu of deregulated cancer cell biology in all its aspects.
Insights
New cancer drug discovery focuses on molecular targets within the complex cellular environment. This approach aims for more effective treatments by considering the whole cancer cell phenotype, moving beyond older methods.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Traditional cancer drug discovery relied on antiproliferative screens for cytotoxic agents for 60 years.
- Newer approaches target specific molecules crucial to cancer development.
- Understanding the cellular environment is vital for effective drug action.
Purpose of the Study:
- To outline a new strategy for cancer drug discovery and development.
- To emphasize a holistic approach considering the entire cancer cell phenotype.
- To integrate understanding of molecular targets with cellular context.
Main Methods:
- Utilizing a cell-based drug discovery screen from the US National Cancer Institute.
- Analyzing over 300 molecular targets and thousands of gene expression patterns.
- Testing molecules with selectivity within the complex cancer cell milieu.
Main Results:
- The study proposes a shift from single-target approaches to a comprehensive view of cancer biology.
- It highlights the importance of considering drug uptake, metabolism, and elimination.
- The National Cancer Institute's screen provides a platform for this integrated approach.
Conclusions:
- A holistic approach to cancer drug discovery is more promising than traditional methods.
- Effective cancer therapeutics require understanding drug action within the complete cellular context.
- Future drug development should focus on molecules active against defined targets within deregulated cancer cell biology.