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Development of resistance mechanisms to the growth-inhibitory effects of transforming growth factor-beta during tumor

J Filmus1, R S Kerbel

  • 1Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.

Current Opinion in Oncology
|January 1, 1993
PubMed

Insights

Cancer cells develop resistance to transforming growth factor-beta's growth-inhibitory effects through progressive, accumulating defects in its signaling pathway during tumor progression. This resistance is a key factor in cancer development.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Transforming growth factor-beta (TGF-β) is a potent inhibitor of epithelial, lymphohematopoietic, and neuroectodermal cell growth.
  • Resistance to TGF-β-mediated growth inhibition is a hallmark of many cancers originating from these cell types.

Purpose of the Study:

  • To review the progressive nature of cancer cell resistance to TGF-β.
  • To explore the diverse molecular mechanisms underlying this resistance.

Main Methods:

  • Literature review focusing on cancer progression and TGF-β signaling.
  • Analysis of studies detailing TGF-β receptor alterations and intracellular signaling defects.

Main Results:

  • TGF-β resistance develops stepwise during tumor progression.
  • Mechanisms include alterations in TGF-β receptors and defects in downstream signaling pathways.
  • Multiple cumulative defects in TGF-β activation, binding, and signaling contribute to resistance.

Conclusions:

  • Progressive accumulation of defects in TGF-β signaling is critical for cancer cell resistance.
  • Understanding these mechanisms is vital for developing targeted cancer therapies.

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