Application of molecular targeted therapies for treatment of gastric cancer and gastroesophageal junction cancer

Abstract

Advanced gastric cancer and gastroesophageal junction (GEJ) cancer still remain serious therapeutic problems. Although palliative chemotherapy compared to the best supportive care prolongs survival of advanced gastric cancer patients, the outcome remains poor and new therapeutic options are warranted. The majority of them are directed towards inhibiting the process of neoangiogenesis or blocking activity of EGF receptors family. The main target of anti-angiogenic therapies are VEGF and its signal transduction pathway. Despite the effectiveness of bevacizumab in some tumors, the phase III trial (AVAGAST) has shown no survival benefit from addition of bevacizumab to standard chemotherapy in gastric cancer. However, in two phase III trials other anti-angiogenicagent ramucirumab in monotherapy (REGARD), and in combination with paclitaxel (RAINBOW) increased overall survival. The discovery of EGFR expression and HER-2 overexpression in gastric cancer cells resulted in attempts to block their activity. The clinical studies including TKIs of EGFR — erlotinib and gefitinib — as well as TKIs of EGFR and HER-2 — lapatinib had disappointing results. Cetuximab, both in monotherapy and in combination with chemotherapy, turned out to be ineffective as well. Trastuzumab combined with chemotherapy in phase III trial (ToGA) prolonged overall survival in patients with overexpression of HER-2. Trastuzumab is the only molecular targeted agent in treatment of gastric cancer patients currently available in Poland.