The treatment of unresectable metastatic colorectal cancer has evolved over the last two decades, as knowledge of cancer biology has broadened and new targets have emerged. ‘The Hallmarks of Cancer’ illustrate the crucial capabilities acquired by cells to become malignant and represent the evolution of knowledge of tumor biology. This review integrates these novel targets and therapies into selected hallmarks: sustaining proliferative signaling, inducing vasculature, avoiding immune destruction, genome instability and mutation, reprogramming cellular metabolism, and resisting cell death. The different strategies and combinations under study are based on treatments with anti-EGFR, anti-VEGF, and anti-HER2 agents, KRAS G12C inhibitors, BRAF and MEK inhibitors, and immune checkpoint inhibitors. However, new approaches are emerging, including vaccines, WEE1 inhibitors, and PARP inhibitors, among others. The further deciphering of cancer biology will unravel new targets, develop novel therapies, and improve patients’ outcomes.

Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy.

Colorectal cancer liver metastases (CRLM) remain a major therapeutic challenge, shaped by marked biological heterogeneity and unpredictable clinical outcomes. While classical Clinical Risk Scores (CRS) continue to inform surgical decision making, their static nature limits their relevance in an era defined by molecular profiling, dynamic biomarkers, and personalized therapy. Advances in genomics and liquid biopsy technologies have expanded the understanding of CRLM beyond traditional clinicopathological parameters, enabling real-time disease monitoring and more refined risk stratification. In parallel, dynamic scoring systems that incorporate evolving clinical and molecular data are redefining how risk is assessed and managed throughout the course of treatment. This review revisits classical CRS, explores emerging molecular and dynamic tools, and discusses their potential integration into clinical practice to improve patient selection, guide treatment timing, and refine the overall management of CRLM.

Background: National trends in sepsis-associated cancer mortality in the USA remain incompletely characterised, particularly regarding long-term structural shifts and their variation across oncologic subpopulations.Methods: We conducted a population-based time-series analysis using the CDC WONDER Multiple Cause of Death database (1999–2020). Cases were defined by an underlying cause of death of malignant neoplasm (ICD-10 codes C00–C97) and a contributing cause of sepsis (A40–A41). We calculated age-standardised mortality rates (ASMR) indexed to the 2000 US Standard Population. Temporal dynamics were assessed using segmented Poisson regression to estimate annual percent changes (APC) and identify structural breakpoints. Furthermore, we employed counterfactual modelling to quantify excess mortality by projecting pre-2010 trends forward, and performed stratified analyses by cancer type (solid vs haematological), sex, and geography.Findings: Of 14 713 914 cancer deaths, 455 369 (3·10%) involved sepsis. Crude mortality increased from 6·26 to 7·94 per 100 000. Segmented regression identified a structural acceleration in the early 2010s, with APCs increasing from 0·47% (95% CI 0·36–0·57) to 2·84% (2·54–3·13). This inflection corresponded to an estimated 31 896 excess deaths compared with historical trends. Crucially, trends diverged by cancer type: mortality declined for haematological malignancies (APC −1·97%; 95% CI −2·21 to −1·73) but surged for solid tumours (APC 2·25%; 95% CI 2·10–2·39). Population ageing accounted for 77·1% of the post-inflection increase; COVID-19 contributions were transient.Interpretation: A structural acceleration in sepsis-associated cancer mortality began in the early 2010s, driven largely by solid tumours and exceeding demographic expectations. This identifies sepsis as a critical, structural determinant of cancer outcomes, necessitating prioritisation within oncologic survivorship guidelines and health system infrastructure.