A variety of pathophysiological mechanisms exist by which physical exercise, nutrition, and the microbiome can impact the development of cancer and the response of tumor cells to systemic anti-cancer therapy. Physical exercise positively impacts the different stages of oncological disease and may improve overall survival and quality of life, reduce treatment-associated toxicity, and improve response to immunotherapy. Nutrition impacts quality of life, and novel nutritional regimens and their role in cancer treatment and outcomes are under active investigation. Finally, the microbiome may act as a predictor of response and resistance to immunotherapy. This comprehensive review delves into the interplay between these elements and their impact on oncological outcomes, emphasizing their role in modulating the immune system and enhancing the response to immunotherapy. The data that support the findings of this study are openly available and referenced in the bibliography section.

Invasive lobular carcinoma (ILC) comprises ∼10%-15% of breast cancers and is characterized by loss of the cell-adhesion molecule E-cadherin (encoded by CDH1), discohesive growth, predominant estrogen receptor (ER) positivity, low-to-intermediate proliferation, and atypical metastatic spread to bone and gastrointestinal/peritoneal sites. Diagnostic assessment is often challenging owing to diffuse infiltration, frequently yielding non-measurable disease per response evaluation criteria in solid tumors (RECIST). Molecularly, ILC is enriched for phosphoinositide 3-kinase (PI3K) activation and harbors emerging vulnerabilities-such as ROS1 synthetic lethality in CDH1-deficient tumors and fibroblast growth factor receptor 1 (FGFR1)/bromodomain and extra-terminal (BET) dependencies-now under study. Because metastatic ILC remains underrepresented in trials, systemic therapy often mirrors invasive ductal carcinoma (IDC). This short communication synthesizes current evidence to distinguish shared from plausibly lobular-specific signals; highlights near-term opportunities-including antibody-drug conjugates (ADCs), oral selective ER degraders (SERDs), and selective use of immunotherapy in an immune-enriched subset with higher tumor-infiltrating lymphocytes (TILs) and PD-L1; and outlines trial-design adaptations-such as incorporating 18F-fluoroestradiol PET (FES-PET)-to improve representation and interpretability in metastatic ILC research.

We report a case of severe, irreversible transverse myelitis following CD19-directed CAR-T cell therapy (axicabtagene ciloleucel) for refractory post-transplant lymphoproliferative disorder (PTLD) in a young female lung-transplant recipient. This case illustrates an emerging neurotoxic complication of CAR-T cell therapy and highlights convergent risk factors including demographics, tumor type and CAR construct. We discuss current evidence of CAR-T–associated myelopathy, its proposed inflammatory and immune-trafficking mechanisms, and the potential contribution of interleukins and chemokines such as IL-1, IL-6, IL-18, CCL-2 and CXCL10 signaling to spinal cord injury. We further address diagnostic challenges, and review current management strategies such as corticosteroids, IL-1 blockade, and IL-6 neutralization. This report underscores the need for heightened vigilance, early imaging, and systematic reporting to improve prevention and treatment of this rare but severe CAR-T–related neurotoxicity.

Background: In Spain, universal coverage is delivered through 17 decentralised Autonomous Communities. We quantified territorial inequality in oncology clinical trial-participation density and examined its ecological association with age-standardised cancer mortality.Methods: We used a longitudinal ecological design with regions as the unit of analysis. Trial-participation density (participants per 100,000 population, 2016-2020) and annual authorised oncology trial counts (2015-2022) came from the Spanish Registry of Clinical Studies. Annual age-standardised cancer mortality came from the Spanish National Statistics Institute. Inequality was described with means, standard deviations, ranges, coefficients of variation, and maximum/minimum ratios. The main analysis used repeated-measures ecological models with calendar-year indicators and region-clustered standard errors, with sensitivity analyses for ageing, population weighting, GDP, post-exposure years, influence, HC3 errors, and wild cluster bootstrap inference.Results: Trial-participation density varied from 0.2 to 41.9 per 100,000 population (mean 15.0, SD 10.5; coefficient of variation 70.2%), a 209-fold regional difference. Mean cancer mortality excluding 2020-2021 varied less (mean 231.5, SD 11.7 per 100,000; coefficient of variation 5.1%). Mean mortality declined from 245.5 per 100,000 in 2015 to 216.5 in 2024. In the year-adjusted repeated-measures model, a 10-unit increase in trial-participation density was associated with -6.6 fewer cancer deaths per 100,000 (95% CI -12.0 to -1.3), equivalent to moving from the lowest to the median regional participation level. After ageing adjustment, the estimate was -5.5 (95% CI -10.3 to -0.7) per 10-unit increase. The post-exposure 2022-2024 analysis preserved the direction and similar magnitude of the association. Population weighting preserved the association, and GDP total attenuated it.Conclusions: In Spain, oncology trial participation is geographically concentrated. Regions with higher trial-participation density had persistently lower ecological cancer mortality, although the association is closely linked with metropolitan scale and oncology-system capacity. Trial infrastructure should be treated as a cancer-equity issue; causal interpretation requires finer geographic and patient-level data.