The investigators hypothesize that the epigenetic agent valproic acid improve the activity of anti-EGFR agents, prevent and revert the emergence of EGFR resistance, in a rechallenge setting.
Correlative mechanistic studies on tissue and blood samples, liquid biopsies, could identify potential biomarkers of efficacy and help understanding the evolutionary dynamics of tumors in response to therapy thus optimizing the treatment approach with a personalized anti- EGFR treatment strategy.
Written informed consent to study procedures and to correlative studies.
Either sex aged ≥ 18.
Histologically proven of colorectal adenocarcinoma.
Diagnosis of metastatic disease.
Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Any contraindication to panitumumab or irinotecan.
Not received immunotherapy if dMMR or MSI-H.
Patients who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid.