Retrospective-prospective observational study in which a novel whole-exome sequencing (WES) approach will be used in association with whole-transcriptome sequencing (WTS) to analyze two independent and equally sized cohorts of patients with mGC.

A workflow specifically designed for this project will be adopted, using clinical outcomes as a benchmark for comparative analyses, to generate a molecular classifier applicable to all patients affected by metastatic gastric cancer mGC and predict atypical tumor responses. Molecular features differently represented in exceptional responders and fast progressors will be monitored by liquid biopsy in patients included in cohort B, consisting of a validation set, leveraging a high-sensitivity technological level that allows to detect both genomic alterations and expression at the transcription level.

In addition, CSCs isolated from fast progressors will be studied with over 1,000 antitumor agents to discover vulnerabilities not currently known.

Inclusion Criteria:

• Age >18 years;
• Histological diagnosis of locally advanced or metastatic gastric cancer (GC) or gastroesophageal junction carcinoma (EJC);
• Adequate biological material for molecular analysis, collected (at surgery or by biopsy) before the administration of any anti-tumor treatment (chemotherapy and/or radiotherapy);
• ECOG PS 0-2;
• Adequate hematological, hepatic and renal function;
• Measurable disease according to RECIST criteria;
• Written informed consent.

Exclusion Criteria:

• Previous chemotherapy for metastatic disease;
• Comorbidities not controlled with adequate medical therapy;
• Brain metastases;
• Patient unable to give adequate consent to the study.

Patients with locally advanced or metastatic inoperable GC who are candidates for first-line chemotherapy and who meet the following criteria.