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Primary and acquired resistance to biologic therapies in gastrointestinal cancers

Sam J Lubner1, Nataliya V Uboha1, Dustin A Deming1

  • 1Department of Medicine, Hematology-Oncology Section, University of Wisconsin Carbone Cancer Center, Madison, WI 53792, USA.

Journal of Gastrointestinal Oncology
|July 25, 2017
PubMed

Insights

Targeted therapies like monoclonal antibodies (mAbs) show promise for gastrointestinal cancers. This review explores resistance mechanisms to VEGF, EGFR, and HER2 inhibitors and discusses ongoing clinical trials to overcome these challenges.

Area of Science:

  • Oncology
  • Gastrointestinal Cancer Research
  • Molecular Targeted Therapy

Background:

  • Advances in cancer biology have spurred therapeutic progress in gastrointestinal cancers.
  • Targeted therapies, including monoclonal antibodies (mAbs) against vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways, have been adopted for colorectal cancers.
  • Human epidermal growth factor receptor 2 (HER2) targeted therapy, like trastuzumab, is standard for HER2-amplified gastroesophageal cancers.

Purpose of the Study:

  • To review innate and acquired resistance mechanisms to VEGF, EGFR, and HER2 targeted therapies in gastrointestinal cancers.
  • To explore ongoing clinical trials aimed at overcoming identified resistance mechanisms.
  • To enhance the efficacy and durability of targeted treatments for gastrointestinal malignancies.

Main Methods:

  • Literature review of existing studies on targeted therapies for gastrointestinal cancers.
  • Analysis of hypothesized and elucidated mechanisms of resistance to specific monoclonal antibodies.
  • Examination of ongoing clinical trials investigating novel therapeutic strategies.

Main Results:

  • Monoclonal antibodies targeting VEGF and EGFR pathways have improved survival in colorectal cancers.
  • Trastuzumab combined with chemotherapy is a standard for HER2-amplified gastroesophageal cancers.
  • Responses to these targeted therapies are not always durable, suggesting resistance mechanisms are at play.

Conclusions:

  • Understanding and overcoming resistance mechanisms are crucial for improving outcomes in targeted gastrointestinal cancer therapy.
  • Ongoing research and clinical trials are essential to retain the therapeutic promise of targeting VEGF, EGFR, and HER2 pathways.
  • Future strategies will focus on combination therapies and novel approaches to circumvent resistance.
Keywords:
Targeted therapygastrointestinal cancersresistance

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