Current therapeutic landscape for advanced gastroesophageal cancers

Abstract

Treatment of advanced gastroesophageal cancers remains challenging for clinicians, patients, and caregivers alike. Despite considerable research, the therapeutic armamentarium is restricted and hardly personalized. In the first-line setting, trastuzumab with a fluoropyrimidine and platinum agent is the standard-of-care in patients with HER2-positive tumor. For the others, a platinum-based doublet (preferably with oxaliplatin) is recommended. Three-drug cytotoxic regimens should be reserved for exceptional cases where patients have good performance status. Triple combinations produce higher toxicity and provide marginal advantage. In the second line setting, the combination of paclitaxel and ramucirumab is preferred over all others. Currently, nothing is approved in the 3 rd or later line. Nivolumab has resulted in an improved benefit in an Asian trial. Early trials of TAS-102, STAT3 inhibitors, anti-claudin 18.2 and other immune checkpoint inhibitors (alone or in combination) are ongoing. However, development of reproducible biomarkers for patient enrichment is critical for future progress.

Chloride intracellular channel 1 promotes esophageal squamous cell carcinoma proliferation via mTOR signalling

“…Esophageal cancer (EC) is a digestive tract cancer associated with significant morbidity, poor prognosis and high mortality. EC has a high incidence in Asian and Middle Eastern countries where it constitutes the sixth most lethal disease with a five-year survival of about 30% [39] . Over 90% of EC patients in China are diagnosed with ESCC, the majority subtype with poor prognosis and high mortality [11] .…”

Survival-associated alternative splicing events interact with the immune microenvironment in stomach adenocarcinoma

“…Early clinical signs and symptoms of STAD might include continuous upper abdominal pain, heartburn, loss of appetite, emesis, and nausea; however, these nonspecific clinical manifestations commonly result in misdiagnosis of STAD[ 20 ]. Most STAD patients progress to advanced stages with symptoms including yellowing of the skin and the whites of the eyes, vomiting, difficulty in swallowing, malnutrition, weight loss, intolerable pain, and blood in the stool[ 21 ]. The development of undiscovered biomarkers could improve the accuracy and specificity of disease prevention, risk prediction, and early diagnosis, promoting a more favorable prognosis in STAD[ 22 ].…”

Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress

“…Generally, for patients with gastric cancer, therapy is combined with cytotoxic chemotherapy and targeted therapy (41). Therefore, it is very important to find a target agent that has synergistic effects while reducing toxicity of cytotoxic agents.…”