Anoikis resistance constitutes a critical pathophysiological mechanism driving metastatic progression in colorectal cancer. While in vitro models are essential for mechanistic studies, conventional 2D cultures inadequately replicate tumor microenvironment (TME) complexity. In this study, we developed a biomimetic composite hydrogel (GHP_4a) composed of 4-arm-PEGDA, Gelatin Methacryloyl, and Hyaluronic acid Methacryloyl to establish compact 3D cell spheres that mimic TME. The GHP_4a demonstrates superior biocompatibility, suitable mechanical strength at 600-700 Pa, and biomimetic properties that promote cell proliferation and differentiation when co-culturing Caco-2 cells. The cell anchorage and survival for anoikis resistance are enhanced compared to traditional 2D cell incubation due to a well-organized 3D formation akin to the extracellular matrix (ECM). The biomimetic mechanism may be attributed to the fact that the GHP_4a promoted the activation of key pro-survival pathways, including FAK and PI3K/Akt signaling, and suppressed caspase-mediated apoptosis. Single-cell RNA sequencing revealed distinct transcriptional profiles within the proliferating T cell population, suggesting a novel regulatory mechanism of T cell-mediated anti-tumor immunity in the TME. Additionally, radiomic analysis identified significant differences in tumor heterogeneity and texture between GHP_4a-based 3D cultures and traditional 2D models. These findings established the GHP_4a as an effective candidate for the in vitro tumor anoikis resistance model, providing a unique approach for studying anoikis resistance in colorectal cancer and offering a robust tool for the development of advancing cancer diagnosis and therapy strategies.

Lung adenocarcinoma remains a leading cause of cancer mortality globally. While immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non-small cell lung cancer (NSCLC), their efficacy in patients with acquired epidermal growth factor receptor (EGFR) T790M mutations following multiline therapy is poorly defined. This case report describes a 52-year-old Asian female never-smoker diagnosed with stage IIIA lung adenocarcinoma. She underwent lobectomy and received multiple lines of therapy. Initial genetic testing showed no EGFR T790M mutation, but subsequent testing after multiline treatment confirmed its acquired presence. Following multiline therapeutic failure, the patient received immunotherapy with cadonilimab (a PD-1/CTLA-4 bispecific antibody). This intervention resulted in disease control, and the patient achieved 9.4 months of progression free survival (PFS). This case suggests that immunotherapy with cadonilimab could be a potential consideration for advanced NSCLC harboring acquired EGFR T790M mutation post-multiline therapy.

Background Nocardiosis is a rare opportunistic infection susceptible to immunocompromised patients. The condition frequently manifests as pulmonary infection and may have imaging characteristics which resemble to lung cancer, such as the nodules and the lymph nodes enlargement, leading to confusion in diagnosis. In addition, Nocardia can also spread through the blood, causing cutaneous and cerebral infections. Case presentation: We report a female patient with long-term oral methylprednisolone and ciclosporin, who had uncommon multiple systemic infections. CT scan showed the patient may be lung cancer with intrapulmonary, subcutaneous and musculature metastases, while the cranial enhanced MRI scan showed brain metastases. Finally, Nocardia was cultured through subcutaneous puncture fluid. After treatment, her multiple organ lesions became significantly smaller or subsided. Conclusions Doctors should consider nocardiosis as a potential infectious disease in patients with compromised immune systems to prevent incorrect diagnosis and treatment.