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Targeted therapies for gastric cancer: failures and hopes from clinical trials

Maria Apicella1, Simona Corso1, Silvia Giordano1

  • 1Department of Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Torino, Italy.

Oncotarget
|September 17, 2017
PubMed

Insights

New treatments are needed for gastric cancer, a leading cause of cancer death. This review examines failed molecular therapies and explores future directions for improving patient survival in gastric cancer treatment.

Area of Science:

  • Oncology
  • Gastroenterology
  • Clinical Trials

Background:

  • Gastric cancer is a significant global health burden, ranking as the third leading cause of cancer mortality worldwide.
  • Current curative options are limited, with surgery being the only definitive treatment and conventional chemotherapy offering minimal survival benefits (median overall survival of 10 months).
  • The limited efficacy of existing treatments highlights the urgent need for novel therapeutic strategies in gastric cancer management.

Purpose of the Study:

  • To review clinical trials of molecular therapies in gastric cancer patients.
  • To analyze the reasons behind the failure of most Phase III clinical trials involving molecular drugs.
  • To identify new perspectives and strategies for improving gastric cancer treatment outcomes.

Main Methods:

  • Systematic review of published Phase III clinical trials evaluating molecular therapies in gastric cancer.
  • Analysis of trial designs, targeted agents (e.g., HER2, VEGFR2 inhibitors), patient populations, and efficacy endpoints.
  • Discussion of potential factors contributing to trial failures, including patient selection, drug resistance, and biological complexity.

Main Results:

  • Only two targeted therapies, Trastuzumab (anti-HER2) and Ramucirumab (anti-VEGFR2), are currently approved for gastric cancer.
  • A majority of Phase III clinical trials investigating molecular drugs in gastric cancer have not met their primary endpoints.
  • The review identifies common challenges and limitations encountered in these trials.

Conclusions:

  • Despite advancements, molecular therapies have shown limited success in improving overall survival for most gastric cancer patients.
  • Understanding the reasons for clinical trial failures is crucial for developing more effective targeted treatments.
  • Future research should focus on personalized medicine approaches, novel drug combinations, and improved patient stratification to enhance gastric cancer therapy.
Keywords:
HER2gastric cancer clinical trialsimmunotherapytargeted therapiestyrosine kinase receptors

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