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Apoptosis by genetic engineering

J Sinkovics1, J Horvath

  • 1Cancer Institute, St. Joseph's Hospital, Tampa, Florida 33607.

Leukemia
|April 1, 1994
PubMed

Insights

Malignant cells often evade apoptosis, or programmed cell death. This study explores targeting apoptosis-resistance in tumors using gene therapy and chemotherapy, highlighting challenges in in vivo transfection.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Apoptosis, a physiological programmed cell death, is often evaded by malignant cells.
  • Genes regulating apoptosis, such as p53 (promoter) and bcl-2, fes (antagonists), are recognized.
  • Tumor cells resistant to apoptosis can still be eliminated by cytotoxic lymphocytes.

Purpose of the Study:

  • To explore therapeutic strategies for overcoming apoptosis resistance in cancer.
  • To investigate the potential of gene therapy and chemotherapy in inducing tumor cell death.
  • To identify challenges and future directions in targeting apoptosis for cancer treatment.

Main Methods:

  • Review of known apoptosis-regulating genes and their roles in cancer.
  • Discussion of lymphocyte-mediated cytotoxicity and apoptosis-inducing cytokines.
  • Exploration of chemotherapeutic agents, particularly topoisomerase inhibitors, in inducing apoptosis.
  • Proposal for cloning and in vivo transfection of apoptotic genes into tumor cells.

Main Results:

  • Malignant cells frequently acquire resistance to apoptosis, a hallmark of cancer.
  • Growth factor/hormone withdrawal can activate apoptosis in dependent tumor cells.
  • Cytotoxic lymphocytes and apoptosis-inducing cytokines show therapeutic potential.
  • Chemotherapeutics, like topoisomerase inhibitors, can induce apoptosis in tumor cells.

Conclusions:

  • Synergistic effects between biologicals and chemotherapeutics in inducing apoptosis are promising.
  • In vivo gene transfer of apoptotic genes into tumors is a proposed strategy.
  • Current limitations in in vivo transfection technology and understanding of apoptosis need to be addressed.

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