Challenges in molecular targeted therapy for gastric cancer: considerations for efficacy and safety

ABSTRACT

Introduction: The Cancer Genome Atlas Research Network recently proposed a molecular classification for gastric cancer (GC) into four subtypes based on comprehensive evaluation. While the mechanisms of molecular targeted therapies in GC were confirmed by multiple clinical studies, only a limited number of therapeutics for GC have been approved to date.

Areas covered: In this systematic review of the available literature, we discuss the completed and ongoing clinical trials of molecular targeted therapies in patients with GC, with a focus on their efficacy and safety profiles.

Expert opinion: Results of recent studies clearly demonstrated that trastuzumab and ramucirumab, monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), respectively, improved overall survival (OS) in GC with manageable safety profiles. Careful surveillance of ongoing clinical trials and timely profiling and monitoring of genetic signatures are imperative to establish a strong foundation for precision medicine in GC.

KEYWORDS:

• Angiogenesis
• gastric cancer
• human epidermal growth factor receptor 2
• molecular diagnosis
• ramucirumab
• targeted therapy
• the Cancer Genome Atlas
• trastuzumab
• vascular endothelial growth factor

Article highlights

• Both the completed and ongoing clinical trials of molecular targeted therapies in patients with GC were discussed, with a focus on their efficacy and safety profiles.

• Trastuzumab and ramucirumab improved overall survival in gastric cancer with manageable safety profiles.

• Careful surveillance of ongoing clinical trials and timely profiling and monitoring of genetic signatures were found to be imperative to establish a strong foundation for precision medicine in GC

• Combination of different targeted therapies may be critical to the success of precision medicine in gastric cancer.

• Management of potential immune-related adverse events is the likely next step in incorporating immunotherapy into the arsenal of precision medicine tools for gastric cancer

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded