Glioma is a fatal brain tumor characterized by rapid proliferation and treatment resistance. Ferroptosis is a newly discovered programmed cell death and plays a crucial role in the occurrence and progression of tumors. In this study, we identified ferroptosis specific markers to reveal the relationship between ferroptosis-related genes and glioma by analyzing whole transcriptome data from Chinese Glioma Genome Atlas, The Cancer Genome Atlas dataset, GSE16011 dataset, and the Repository of Molecular Brain Neoplasia Data dataset. Nineteen ferroptosis-related genes with clinical and pathological features of glioma were identified as highly correlated. Functional assays in glioma cell lines indicated the association of ferroptosis with temozolomide resistance, autophagy, and glioma cell migration. Therefore, the identified ferroptosis-related genes were significantly correlated with glioma progression.

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Protein/peptide drugs possess unique advantages, such as high pharmacological potency, molecular specificity, multifunctionality, and low toxicity, and thus hold great potential for use in cancer therapy. In the past decades, great achievements have been made in protein delivery systems, which can protect cargo proteins against detrimental physiological environments and efficiently deliver proteins into tumor sites and cells. In this Review, we first summarize the existing protein/peptide drugs used for cancer treatment, illustrate their anti-tumor mechanisms, and point out the potential challenges/barriers against their medical utility. We then discuss the existing strategies for protein encapsulation/conjugation and survey recent advances in the development of protein delivery vehicles, including lipid-based membrane nanocarriers, polymeric carriers, metal–organic frameworks, inorganic carriers, protein/peptide-based nanocarriers, and DNA nanostructures. The design strategies, advantages in potentiating protein delivery efficiencies, and possible limitations of these delivery systems are also discussed. Finally, future opportunities and challenges in anti-cancer protein/peptide delivery are indicated.

Tumor relapse after chemotherapy is a major hurdle for successful cancer therapy. Chemotherapeutic drugs select for resistant tumor cells and reshape tumor microenvironment, including the blood supply system. Using animal models, we observed on macrophages in tumor tissue a close correlation between upregulated Tie2 expression and tumor relapse upon chemotherapy.

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