Differential expression of cell adhesion genes: Implications for drug resistance

Wilfred D. Stein*, Thomas Litman, Tito Fojo, Susan E. Bates

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

14 Scopus citations

Abstract

It is well known that tumors arising from tissues such as kidney, pancreas, liver and stomach are particularly refractory to treatment. Searching for new anticancer drugs using cells in culture has yielded some effective therapies, but these refractory tumors remain intractable. Studies that compare cells grown in suspension to similar cells grown attached to one another as aggregates have suggested that it is adhesion to the extracellular matrix of the basal membrane that confers resistance to apoptosis and, hence, resistance to cytotoxins. The genes whose expression correlates with poor survival might, therefore, act through such a matrix-to-cell suppression of apoptosis. Indeed, correlative mining of gene expression and patient survival databases suggests that poor survival in patients with metastatic cancer correlates highly with tumor expression of a common theme: the genes involved in cell adhesion and the cytoskeleton. If the proteins involved in tethering cells to the extracellular matrix are important in conferring drug resistance, it may be possible to improve chemotherapy by designing drugs that target these proteins.

Original languageEnglish
Pages (from-to)861-865
Number of pages5
JournalInternational Journal of Cancer
Volume113
Issue number6
DOIs
StatePublished - 1 Mar 2005

Keywords

  • Cell adhesion
  • Database mining
  • Drug resistance
  • Gene expression
  • Metastasis
  • Surveillance, Epidemiology and End Results data

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