Targeted therapies in gastric cancer and future perspectives

Abstract

Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.

Subtraction of Epstein–Barr virus and microsatellite instability genotypes from the Lauren histotypes: Combined molecular and histologic subtyping with clinicopathological and prognostic significance validated in a cohort of 1,248 cases

“…31 The CIN subtype, which are primarily of the intestinal type, shows frequent TP53 mutations, ERBB2, VEGFA or other receptor tyrosine kinase amplifications that could be ameliorated by trastuzumab, ramucirumab or other receptor tyrosine kinase-targeted therapies. 32 A recent study indicated that patients with CIN tumors might experience the greatest benefits from adjuvant chemotherapy (HR, 0.39; 95% CI, 0.16-0.94; p = 0.03). 33 However, our study found all subtypes exhibited survival improvement after chemotherapy although the EBV-associated and D/M cases had more durable response to chemotherapy.…”

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

“…The treatment plan within physician's options includes surgery, chemotherapy, radiation or other anticancer drugs. However, despite multiple therapeutic choices, the survival rate of patients with advanced gastric cancer remains poor in last several decades [3]. To facilitate optimal therapeutic strategies for gastric cancer is still a challenge for clinical application.…”

Analysis of systemic immunity and inflammation in the prognosis of gastric adenocarcinoma

“…новых случаев РЖ, что составляет более 11 % всех злокачественных опухолей [3]. По данным O. Yazici и соавт., 5-летняя общая выживаемость (ОВ) пациентов с РЖ в мире в 2016 г. составила не более 20-30 % [4]. В то же время при местно-распространенных опухолях примерно в 50 % случаев после адъювантного лечения наблюдается местный / системный рецидив, и 5-летняя ОВ достигается только в 10-15 % случаев [5].…”

“…Несмотря на то что агрессивная хирургическая тактика и расширенные операции являются стандартом, при котором можно добиться полного излечения, с воздействием на предположительно существующие даже на ранних стадиях имплантационные или гематогенные метастазы с помощью адъювантной, неоадъювантной, регионарной, внутриполостной химиотерапии, результаты все еще довольно скромны. Поэтому понятны стремления ученых найти «ключ» к пониманию возможностей патогенетической регуляции процессов роста и дифференцировки злокачественной клетки [4].…”