Neuroendocrine prostate cancer (NEPC) is a rare entity representing 1% of all prostate malignancies, associated with poor prognosis and often concomitant with paraneoplastic syndromes such as Cushing's syndrome (CS) with ectopic adrenocorticotropic hormone (ACTH) production. We present a case of a 56-year-old man with recent lower urinary tract symptoms hospitalized for pelvic pain, rectal tenesmus, and fatigue. A CT scan documented a large prostatic mass, adenomegalies, and hepatic lesions. Bone scintigraphy showed dispersed osteoblastic metastization. The patient had uncontrolled hypertension and hypokalemia that lead to the diagnosis of paraneoplastic ACTH-dependent CS. Prostate biopsy confirmed small cell NEPC. Potassium supplementation, anti-hypertensive medication, and metyrapone were initiated. The patient was proposed for palliative chemotherapy but died within a few days from a urinary tract infection. The authors aim to draw attention to a case of paraneoplastic CS, a rare manifestation, within the rarity that is NEPC.

Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine.

Synchronous pleural mesothelioma (PM) and breast cancer are extremely rare. We present the case of a 53-year-old female diagnosed with localized breast cancer. She was radically treated with surgery, but during the adjuvant radiotherapy, the patient developed fever and dyspnoea, and pleural thickening was found on a CT scan. The biopsy confirmed the diagnosis of a synchronous malignancy - pleural epithelioid mesothelioma. The patient stopped radiotherapy and started adjuvant endocrine therapy with exemestane, a third-generation aromatase inhibitor, with an unexpected partial response to the PM. The patient remains on exemestane with a sustained partial response. This is a rare case of synchronous tumours that show a real-life benefit of exemestane in the treatment of pleural mesothelioma, which was only described in vitro, with a good sustained response. This suggests a potential for exemestane in the treatment of mesothelioma, which is an aggressive form of cancer with few therapeutics with sustained results.

Cancer remains a highly complex and heterogeneous disease, causing major morbidity and mortality worldwide despite advances in diagnosis and treatment. The hallmarks of cancer enlighten the biological mechanisms supporting tumourigenesis and malignant evolution, while helping to identify potential therapeutic targets. Medical cannabis has mostly been used in oncology for supportive care, but increasing preclinical evidence suggests interference with cancer-related signalling pathways. This narrative review summarizes the current evidence on cannabinoids, in particular the phytocannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), framing their prospective anticancer effects in the hallmarks of cancer. Preclinical studies imply that CBD exerts antiproliferative effects by modulating oncogenic signalling pathways, including EGFR, PI3K/AKT, RAS/RAF/ERK, mTOR and Wnt/β-catenin, while also influencing tumour suppressor pathways involving p53, p21 and p27, causing cell cycle arrest. CBD has additionally been shown to promote programmed cell death via mitochondrial dysfunction and autophagy, altering cancer metabolism as well. Furthermore, CBD has shown anti-invasive and antiangiogenic properties and also appears to modulate immune responses and interactions with the tumour microenvironment, including emerging links with the microbiome. Overall, cannabinoids exhibit biologically plausible antitumour activity across multiple cancer hallmarks and may present promising candidates for combination therapeutic strategies. Nonetheless, the current evidence remains predominantly preclinical, and robust translational studies and clinical trials are needed to clarify their pharmacokinetic and pharmacodynamic profiles, determine their clinical efficacy and safety while assessing their potential integration into multimodal cancer treatment.

In the non-small-cell lung cancer (NSCLC) subtype, adenocarcinoma is the most common histology. The choice of first-line treatment depends on the mutational status. We present a case of a 54-year-old non-smoker woman with lung adenocarcinoma and extensive metastatic disease at diagnosis. The genetic analysis demonstrated a sensitizing epidermal growth factor receptor (EGFR) exon 19 mutation and she began treatment with a first-generation EGFR tyrosine kinase inhibitor (TKI), erlotinib. Due to successively acquired resistances and disease progression, six treatment lines were pursued, including third-generation EGFR TKI and chemotherapy. The patient accomplished an overall survival of 47 months. This case emphasized the importance of monitoring tumor mutational alterations, allowing us to implement a multi-line treatment. Targeted therapy in advanced NSCLC largely improved the overall survival of these patients.