New agents on the horizon in gastric cancer

• Published in: Annals of oncology Vol. 28; no. 8; pp. 1767 - 1775
• Main Authors: Lordick, F., Shitara, K., Janjigian, Y.Y.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2017
• Subjects: Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; Claudin 18.2; DNA Damage; DNA Repair; gastric cancer; HER2; Humans; Immunotherapy; Neoplastic Stem Cells - drug effects; STAT3; stem cell inhibition; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - therapy; Tumor Microenvironment; Claudin 18.2; gastric cancer; HER2; immunotherapy; STAT3; stem cell inhibition
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdx051

Conventional cytotoxic chemotherapy has been the backbone of advanced gastric cancer treatment for decades and still represents a key element of the therapeutic armamentarium. However, only small increments in survival outcomes have been reached. A better understanding of genetic alterations and molecular signatures of gastric cancer has been reached in the last years. It will serve as a roadmap for better treatment stratification and future drug development. We reviewed preclinical and clinical studies that assessed novel treatment targets and emerging drug therapies in gastric cancer. We performed research via PubMed, and the congress webpages of the American Society of Clinical Oncology, European Society of Medical Oncology and the Japanese Society of Medical Oncology. HER2-targeting with trastuzumab is effective in HER2-positive metastatic gastric cancer; combined HER2 targeting strategies are being investigated. Studies assessing the role of HER2 targeting in the perioperative setting are ongoing. Novel treatment targets include inhibition of cancer stemness-related signaling pathways like STAT3. DNA damage repair and Claudin 18.2, a tight junction protein with high expression in gastric cancers are also novel molecular drug targets. Modification of the tumor microenvironment, including activation of immune response by PD-1/PD-L1 checkpoint inhibitors and stroma modification by matrix metalloproteinase-9 inhibition, led to first promising treatment results. Novel treatment options for gastric cancer patients are emerging. They involve novel mechanisms of action, and are based on our constantly increasing understanding of tumor biology and better molecular stratification of gastric cancer patients.