The role of targeted therapy for gastrointestinal tumors

Abstract

Many targeted drugs have been studied to target the molecular pathways involved in the development of gastrointestinal cancers. Anti-VEGF, anti-EGFR agents, and recently also multi-kinase inhibitor regorafenib, have already been available for the treatment of metastatic colorectal cancer patients. To date, Her-2 positive, gastric cancer patients, are also treated with trastuzumab, while the multi-targeted inhibitor, sorafenib, represents the standard treatment for hepatocellular carcinoma patients. Finally, sunitinib and everolimus, have been approved for the treatment of the neuroendocrine gastroenteropancreatic tumors. Actually a great number of further drugs are under preclinical and clinical development. The aim of this review is to provide a comprehensive overview of the state of art, focusing on the new emerging strategies in the personalized treatment of gastrointestinal tumors.

Keywords::

• colorectal cancer
• gastric cancer
• gastrointestinal tumors
• hepatocellular carcinoma
• neuroendocrine tumors
• targeted therapy

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The introduction of targeted therapies radically changed the approach of oncologists in the treatment of the cancers of the gastrointestinal tract.

• The addition of anti-VEGF, bevacizumab and anti-EGFR, cetuximab/panitumumab, to chemotherapy, significantly improved the survival rates of metastatic colorectal cancer patients.

• Both small molecules and antibodies showed activity in other gastrointestinal (GI) tumors, such as gastric, neuroendocrine tumors and hepatocellular carcinoma and are already available for clinical use in everyday practice.

• We now have molecular markers, whose identification has become mandatory for proper treatment planning in oncology.

• First KRAS and more recently RAS testing influence dramatically our treatment algorithm in metastatic colorectal cancer.

• A great number of new targeted agents are actually under preclinical and clinical development (i.e., MET inhibitors, MEK inhibitors, etc.). Furthermore, an antibody–drug conjugate, such as trastuzumab emtansine, is under preclinical investigation in HER2-positive gastric cancer cell lines in vitro and in vivo.

• Some of these new drugs, which are under development, were studied to improve the effects of previous agents on targets whose impairments have been already known to be related to cancer development and progression.

• Researchers worldwide are looking for further molecular pathways involved in GI tumors and a great number of new targeted agents are actually under investigation.

• Nowadays, targeted therapy is part of daily life of patients and physicians who treat those patients with GI tumors, but much more progress can be made.