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Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Seiichiro Mitani1, Hisato Kawakami1

  • 1Department of Medical Oncology, Faculty of Medicine, Kindai University, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.

Cancers
|February 14, 2020
PubMed

Insights

Trastuzumab improves survival for HER2-positive advanced gastric cancer, but resistance is a challenge. New antibody-drug conjugates show promise for overcoming treatment resistance.

Area of Science:

  • Oncology
  • Gastroenterology
  • Immunotherapy

Background:

  • Trastuzumab, a HER2-targeted monoclonal antibody, has improved survival in HER2-positive advanced gastric or gastroesophageal junction cancer (AGC).
  • Resistance to trastuzumab is an inevitable challenge, with strategies effective in breast cancer failing in AGC.
  • Understanding resistance mechanisms is crucial for developing new treatments for HER2-positive AGC.

Purpose of the Study:

  • To review mechanisms of resistance to HER2-targeted therapy in AGC.
  • To outline challenges in treating trastuzumab-refractory HER2-positive AGC.
  • To describe novel therapeutic agents for HER2-positive AGC.

Main Methods:

  • Literature review of mechanisms of resistance to HER2-targeted therapy.
  • Analysis of clinical challenges in trastuzumab-refractory HER2-positive AGC.
  • Summary of emerging HER2-targeted agents, including antibody-drug conjugates.

Main Results:

  • Several mechanisms contribute to trastuzumab resistance in HER2-positive AGC.
  • Treatment strategies successful in breast cancer have not translated to clinical benefit in AGC.
  • Novel agents, such as HER2 antibody-drug conjugates, demonstrate promising antitumor activity in early studies.

Conclusions:

  • Trastuzumab resistance remains a significant hurdle in HER2-positive AGC treatment.
  • Further research into resistance mechanisms is needed.
  • HER2 antibody-drug conjugates represent a promising new therapeutic avenue for patients refractory to trastuzumab.
Keywords:
AGCHER2gastric cancerresistancetrastuzumab

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