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Anticancer medicines in development: assessment of bioactivity profiles within the National Cancer Institute

David G Covell1, Ruili Huang, Anders Wallqvist

  • 1National Cancer Institute-Frederick, Developmental Therapeutics Program, Screening Technologies Branch, Laboratory of Computational Technologies, Frederick, MD 21702, USA. covell@ncifcrf.gov

Molecular Cancer Therapeutics
|August 19, 2007
PubMed

Insights

This study analyzed anticancer drugs in clinical trials against National Cancer Institute (NCI) data. The NCI anticancer screen effectively predicts drug sensitivity for leukemia, colon, CNS, melanoma, and ovarian cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Bioinformatics

Background:

  • Anticancer drug development relies on preclinical screening.
  • The National Cancer Institute (NCI) 60 cell line panel is a key resource for anticancer drug screening.
  • Understanding the predictive value of the NCI screen for clinical trial outcomes is crucial.

Purpose of the Study:

  • To analyze the correlation between NCI anticancer screening results and the clinical trial status of anticancer compounds.
  • To determine if NCI 60 cell line panel sensitivity predicts clinical efficacy for specific cancer types.
  • To explore the use of structural analogues and 2D features for refining compound selection based on NCI screening data.

Main Methods:

  • Analysis of anticancer compounds in Phase I-III clinical trials.
  • Examination of bioactivity profiles from the NCI anticancer screening program (NCI 60 cell lines).
  • Correlation analysis between NCI panel sensitivity and proposed clinical cancer types.
  • Application of 2D structural features for compound selection refinement.

Main Results:

  • Strong support for using the NCI screen to select analogues sensitive to leukemia, colon, central nervous system, melanoma, and ovarian cancer panels.
  • Limited support for using the NCI screen for renal, prostate, and breast cancer panels.
  • Demonstrated utility of 2D structural features in refining compound selection based on tumor panel sensitivity.

Conclusions:

  • The NCI anticancer screen is a valuable tool for predicting drug sensitivity in specific cancer types (leukemia, colon, CNS, melanoma, ovarian).
  • The screen's predictive power is less robust for renal, prostate, and breast cancers.
  • Integrating NCI screening data with structural analysis can enhance the selection of promising anticancer drug candidates.

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