The study is aimed at patients with advanced cancer and EGFR mutation. Some molecules recently discovered at the level of tumor tissue can influence the response to anti-EGFR drugs. Among these molecules is NRG1, which binds to the EGFR receptor family.

Unravelling the mechanisms that give cancer cells resistance to such biologics could improve response to therapy and survival. And analyzing tumors during anti-EGFR drug therapy used in clinical practice could allow us to perform analyses on NRG1 and hypothesize a possible strategy to increase survival

Experimental, tissue study. Patients with EGFR receptor amplification/overexpression or activating mutations treated with anti-EGFR cancer therapies will be involved in the study as required in normal clinical practice. Clinical information of the patients, relevant to the conduct of the study, will be collected: age, sex, ethnicity, smoking habit, diagnosis, staging of the tumor, site of any metastases, possible presence of ascites and/or pleural effusion, type of oncological therapy administered, concomitant therapies, radiological re-evaluation of the tumor, response to treatment, survival.

Similarly, peripheral blood, tissue obtained from archival tumor biopsies, ascitic and/or pleural fluid samples (taken, if present, as per clinical practice) will be collected. Primary cell cultures will be derived from tumor biopsies, ascites, and/or pleural effusion for in vitro studies The lymphocyte population will be isolated from the peripheral blood of patients

Inclusion Criteria:

• patients aged ≥ 18 years
• patients with advanced cancer characterized by amplification/overexpression or activating mutations of the EGFR receptor.
• patients who are candidates for treatment with TKI and/or mAbs both in the first and second line, according to clinical practice.
• possibility of obtaining all information relating to the clinical history - obtaining written informed consent

Exclusion Criteria:

• Patients who in the opinion of the investigator may not be compliant with the needs of the study
• patients suffering from pathologies (e.g. psychiatric, neurological) that do not allow the obtaining of valid informed consent

Patients who have EGFR receptor amplification/overexpression or activating mutations, either responsive to anti-EGFR therapy (TKIs or mABs) or recurrent despite anti-EGFR therapy (TKIs or mABs), will be enrolled in the study.