Targeted therapy in gastric cancer: Personalizing cancer treatment based on patient genome

Abstract

Gastric cancer is the second leading cause of cancer-related deaths worldwide. Conventional cytotoxic chemotherapy has limited efficacy for metastatic gastric cancer, with an overall survival of approximately ten months. Recent advances in high-throughput technologies have enabled the implementation of personalized cancer therapy for high-risk patients. The use of such high-throughput technologies, including microarray and next generation sequencing, have promoted the discovery of novel targets that offer new treatment strategies for patients lacking other therapeutic options. Many molecular pathways are currently under investigation as therapeutic targets in gastric cancer, including those related to the epidermal growth factor receptor family, the mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin factors. Advances in molecular diagnostic tools further support the discovery of new molecular targets. Limitations exist, however; not all patients can be tested for biomarkers, and numerous challenges hamper implementation of targeted therapy in clinical settings. Indeed, the scale of tumor genomic profiling is rapidly outpacing our ability to appropriately synthesize all the information in order to optimally refine patient care. Therefore, clinicians must continue to educate themselves regarding new tools and frameworks, and to utilize multidisciplinary team science, comprised of oncologists, geneticists, pathologists, biologists and bioinformaticians, to successfully implement this genomic approach therapeutically.

Keywords: Gastric cancer, Targeted therapy, Biomarker, Microarray, Sequencing

Core tip: Understanding the molecular mechanisms governing carcinogenesis, progression and prognosis of gastric cancer is a prerequisite for development of effective management strategies. Analysis of genomic and proteomic expression profiles of oncogenic signaling pathways have revealed different molecular subtypes of gastric cancer. Development of personalized cancer therapy regimens will specifically target aberrations that drive tumor growth and survival. Therefore, identifying and administering the appropriate drug based on genetic profiling will improve clinical outcomes and decrease toxicity. We anticipate that identification of novel cancer targets will further aid in understanding of cancer heterogeneity and in refinement of personalized therapeutic strategies.