Intrabodies pp 129-146 | Cite as

Intracellular Targeting of Oncogenes: A Novel Approach for Cancer Therapy

  • Olivier Cochet
  • Isabelle Delumeau
  • Mireille Kenigsberg
  • Nadège Gruel
  • Fabien Schweighoffer
  • Laurent Bracco
  • Jean Luc Teillaud
  • Bruno Tocque

Abstract

It is now well established that cancer is a multistep disease. In the case of colon cancer, we know of at least five steps in the process of moving from a normal cell to a tumor cell.1 Each step occurs at a very low frequency but can be accelerated or obviated by environmental or genetic factors. This process may be explained at a molecular level by the need for a tumor cell to sustain several mutations in its genome, each of which is required to alter a distinct target whose activation yields a subset of the phenotypic changes necessary for conversion to the fully tumorigenic state. Are there as many distinct mechanisms of transformation as there are oncogenes? In vitro and in vivo experiments showed that there are two central cellular growth regulatory pathways that must be disrupted in order for the cell to proceed to full oncogenic transformation. There is ample testimony to the fact that oncogenic retroviruses carrying single oncogenes are potently tumorigenic. The biological model of two genetic changes required for transformation is best exemplified by the cooperation between the ras and p53 genes2 and provides a challenge to those studying the biochemistry of their encoded proteins. How can the biological effects of such mutated proteins be circumvented to induce tumor regression? Strategies for neutralizing the effects of these proteins by expressing synthetic genes in target tumors can now be envisioned. We will discuss in this chapter some of the approaches aimed at blocking the oncogenic functions of genes such as ras, and at neutralizing the oncogenic function of the p53 mutant forms using single chain antibodies.

Keywords

Toxicity Shrinkage Oncol Sarcoma Progesterone 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Olivier Cochet
  • Isabelle Delumeau
  • Mireille Kenigsberg
  • Nadège Gruel
  • Fabien Schweighoffer
  • Laurent Bracco
  • Jean Luc Teillaud
  • Bruno Tocque

There are no affiliations available

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