The clinical and molecular heterogeneity of IBD-both between patients and within the same individual over time-continues to pose a significant challenge to the implementation of truly personalised treatment strategies. Unlike oncology, where somatic mutation patterns define an actionable information layer, IBD lacks detectable dominant molecular drivers that can guide therapeutic choices. Although the therapeutic landscape has broadened with the advent of numerous biologics and small molecule drugs, predictive (ex ante) biomarkers for treatment response remain elusive. In this review, we assess the current progress and limitations of biomarker-guided precision therapy in IBD. We argue that traditional binary response definitions at single landmark endpoints fail to reflect the multidimensional and dynamic nature of therapeutic outcomes. We hence propose combined, and thus individualised, endpoints such as comprehensive disease control as a more holistic and responsive therapy goal in IBD. We propose to integrate the individual longitudinal dynamics of treatment response, and also continuous, objective monitoring of subclinical residual inflammation, analogous to the concept of minimal residual disease in oncology. In this concept, longitudinal assessment of patient-reported outcomes and molecular profiling in response to therapy may serve as early predictors of long-term outcomes, guide early therapeutic adjustments and reveal mechanisms that open new therapeutic avenues, such as adjunct or combination treatments. Adopting this dynamic, data-driven approach to treatment adaptation could shift management of IBD from reactive to proactive and substantially improve long-term outcomes with the vision to fully control a life-long disease.

Colorectal cancer (CRC) is one of the most common malignant cancers and its incidence is steadily rising particularly in young patients. While screening measures and the widespread availability of surgical treatment have led to an impressive improvement of prognosis within the overall CRC population, patients with metastatic CRC still face 5-year survival rates of around 10-25%. Despite continuous development of new systemic treatment strategies that include cytotoxic chemotherapy and targeted therapy, most patients with metastatic CRC eventually progress. However, a small proportion of patients with mismatch repair-deficient or microsatellite unstable CRC responds exceptionally well to treatment with immune checkpoint inhibitors, thereby proving that CRC is in principle amenable to immunotherapy and showing that long-term disease stabilisation can be achieved even in metastasised stages. However, the reasons for the lack of response to immunotherapy in the vast majority of CRC cases remain to be elucidated. Yet, recent evidence suggests that the tumour stroma, which includes non-immune cells in the colorectal tumour microenvironment, mediates immunosuppressive mechanisms that prevent effective immunotherapy. These findings open new avenues for the development of advanced immunotherapies for CRC. In this review, we summarise major developments in the systemic therapy of CRC within the last couple of decades, provide an overview of emerging and soon-to-be implemented therapeutic strategies and present concepts from clinical and preclinical research to manipulate tumour cells and the tumour stroma to sensitise microsatellite stable colorectal tumours to immunotherapy.

Dipeptidyl peptidase-4 inhibitors (DPP-4is) have been reported to exhibit therapeutic effects in Parkinson's disease (PD), increasing their potential for drug repurposing. One aspect of PD pathogenesis is thought to be associated with the gut-brain axis, where α-synuclein from the gut is transmitted to the brain via the vagus nerve (VN).

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited treatment options and poor prognosis, especially for patients who failed standard therapies.

Obesity-related alterations in the gut microbiota have been linked to cognitive decline, yet their relationship with attention remains poorly understood.

Diffuse gastric cancer (DGC) is the most common manifestation in germline CTNNA1 variant carriers, with one study estimating a 49-57% lifetime risk by age 80. Knowledge on CTNNA1-associated hereditary diffuse gastric cancer (HDGC), loss-of-function mechanisms, variant-type causality, disease spectrum and cancer risks remains scarce.

Although surgical gastrojejunostomy (SGJ) is the standard method for palliation of gastric outlet obstruction (GOO), an endoscopic method-endoscopic ultrasound-guided gastroenterostomy (EUS-GE)-has been proposed as a novel, less invasive approach.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, largely due to the limited efficacy of current therapies in advanced stages of the disease. Most cases of HCC develop in the setting of chronic liver disease, particularly cirrhosis, where ongoing cycles of inflammation, hepatocyte death and regeneration foster the gradual accumulation of genetic and epigenetic alterations that promote malignant transformation. These molecular changes contribute to the high degree of tumour heterogeneity observed in HCC, a major factor underlying resistance to current treatments. As a result, sustained clinical responses to existing therapies, such as tyrosine kinase inhibitors, anti-angiogenic agents and immune checkpoint inhibitors, remain uncommon. In this context, a growing body of evidence has identified epigenetic dysregulation as a key driver of tumour progression and therapeutic resistance, highlighting a new frontier for intervention. This review provides clinicians and researchers with a comprehensive overview of the emerging field of epigenetic therapies in HCC, summarising results from both completed and ongoing clinical trials involving the so-called 'epidrugs'. Importantly, we discuss how targeting epigenetic mechanisms may not only suppress tumour growth but also enhance the effectiveness of current therapies by reversing resistance pathways. By translating complex molecular insights into tangible therapeutic strategies, epigenetics is poised to reshape the future of HCC management, offering renewed hope for more durable and personalised treatment responses in a disease where progress is urgently needed.