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Modulation of tumor radiation response with G3139, a bcl-2 antisense oligonucleotide

Nicole Wiedenmann1, Masashi Koto, Uma Raju

  • 1Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Unit 066, Houston, TX 77030-4009, USA.

Investigational New Drugs
|May 12, 2007
PubMed

Insights

Bcl-2 antisense oligonucleotide (AS ODN) G3139 enhanced radiation therapy effects in bcl-2 positive colon tumors. This combination showed promise for improving radiotherapy outcomes in specific cancer types.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • Overexpression of anti-apoptotic bcl-2 protein is linked to cancer therapy resistance.
  • Bcl-2 antisense (AS) treatment combined with chemotherapy is clinically validated.
  • The combination of bcl-2 AS with radiotherapy has not been previously investigated.

Purpose of the Study:

  • To evaluate the in vivo anti-tumor effects of combining radiation therapy with the bcl-2 targeted AS oligonucleotide (ODN) G3139 (Oblimersen Sodium).

Main Methods:

  • Two human colon carcinoma cell lines (SW620, bcl-2 positive; HT-29, bcl-2 negative) were grown as xenografts.
  • The response to combined bcl-2 AS/radiation treatment was assessed.
  • Tumor growth delay and radiocurability (TCD50 assay) were measured.

Main Results:

  • G3139 significantly potentiated the radiation response in bcl-2 positive SW620 tumors, as measured by tumor growth delay.
  • G3139 had no significant effect on bcl-2 negative HT-29 tumors.
  • The enhancement in tumor growth delay did not translate to improved tumor cure rates for SW620 xenografts.
  • A control ODN (G3622) showed no effect, indicating a sequence-specific effect of G3139.

Conclusions:

  • Combined bcl-2 AS (G3139) and radiation therapy can enhance tumor growth delay in bcl-2 positive tumors.
  • This combination strategy warrants further investigation for specific cancer indications.
  • The efficacy appears to be dependent on bcl-2 expression and ODN sequence specificity.

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