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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Targeted therapy in rectal cancer

Christopher G Willett1, Dan G Duda, Brian G Czito

  • 1Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27705, USA. christopher.willett@duke.edu

Oncology (Williston Park, N.Y.)
|October 4, 2007
PubMed

Insights

Targeted therapies like cetuximab (anti-EGFR) and bevacizumab (anti-VEGF) show promise in treating colorectal and rectal cancers. Combining these agents with radiation and chemotherapy may improve patient outcomes.

Area of Science:

  • Oncology
  • Gastroenterology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are overexpressed in colorectal cancer, correlating with poor prognosis.
  • Anti-EGFR (cetuximab) and anti-VEGF (bevacizumab) therapies are established in metastatic colorectal cancer treatment.
  • Retrospective studies suggest EGFR-expressing rectal cancer patients undergoing neoadjuvant chemoradiation have worse outcomes.

Purpose of the Study:

  • To review completed and ongoing trials investigating anti-EGFR and anti-VEGF agents in rectal cancer.
  • To evaluate the rationale for combining cetuximab with neoadjuvant chemoradiation in rectal cancer.
  • To explore the mechanisms of VEGF-targeted therapy, including tumor vessel damage and radiosensitization.

Main Methods:

  • Review of clinical trial data for anti-EGFR and anti-VEGF agents in colorectal and rectal cancers.
  • Analysis of preclinical models demonstrating synergy between EGFR inhibitors and radiation.
  • Examination of the impact of VEGF blockade on tumor vasculature and drug penetration.

Main Results:

  • Cetuximab is approved for metastatic colorectal cancer and shows potential in neoadjuvant rectal cancer settings.
  • Bevacizumab, an anti-VEGF agent, is used in metastatic colorectal cancer and may enhance radiosensitivity.
  • VEGF blockade can normalize tumor vasculature, improving oxygenation and treatment efficacy.

Conclusions:

  • There is a strong rationale for combining cetuximab with neoadjuvant chemoradiation in rectal cancer.
  • VEGF-targeted therapies offer potential benefits in rectal cancer by damaging tumor vasculature and increasing radiosensitivity.
  • Ongoing trials are crucial for clarifying the role of these targeted agents in rectal cancer treatment.

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