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The incidence of gastroesophageal cancers is rising, driven, in part, by an increasing burden of risk factors of obesity and gastroesophageal reflux. Despite efforts to address these risk factors, and a growing interest in methods of population screening, the bulk of these tumours are unresectable at diagnosis. In this setting, effective systemic treatments are paramount to improve survival and quality of life.

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Carcinoma of unknown primary (CUP) is a diverse group of malignancies characterized by metastatic disease without an identified primary site. It typically presents with a poor prognosis due to widespread metastasis at diagnosis. This report discusses a 58-year-old female patient with advanced CUP and diffuse liver metastasis.

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The most common histological subtypes of endometrial cancer consist of endometrioid and uterine serous carcinoma, with the latter being more aggressive and accompanied by poor prognosis. Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor associated with cell proliferation, differentiation, and survival. HER2 positivity can be diagnosed in many solid tumors.

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Patients diagnosed with metastatic colorectal cancer (mCRC) have a poor prognosis with survival ranging 2-3 years. The prevalence of human epidermal growth factor receptor 2 (HER2) amplification is approximately 3-4% in mCRC and increases up to 8% in patients with // wild-type (WT) CRC tumors. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor that, in combination with trastuzumab, has demonstrated clinically meaningful activity in patients with chemotherapy-refractory, HER2-positive (HER2+), WT mCRC in the MOUNTAINEER trial.

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Purpose: HER2 inhibition represents a therapeutic approach with proven clinical efficacy in gastric cancer. However, resistance against HER2-directed therapeutics highlights the need for alternative approaches or drug combinations. Histone deacetylase inhibitors (HDACi) display a broad spectrum of antitumor properties, which may include effects on receptor tyrosine kinases.

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