Lipid rafts, caveolae, and epidermal growth factor receptor family: friends or foes?

Lipid rafts are dynamic microdomains enriched with cholesterol and sphingolipids that play critical roles in cellular processes by organizing and concentrating specific proteins involved in signal transduction. The interplay between lipid rafts, raft-associated caveolae and the human epidermal growth factor receptors has significant implications in cancer biology, particularly in breast and gastric cancer therapy resistance. This review examines the structural and functional characteristics of lipid rafts, their involvement in EGFR and HER2 signaling, and the impact of lipid rafts/CXCL12/CXCR4/HER2 axis on bone metastasis. We also discuss the potential of targeting lipid rafts and caveolin-1 to enhance therapeutic strategies against HER2-positive cancers and the impact of co-localization of trastuzumab or antibody drug conjugates with caveolin-1 on therapy response. Emerging evidence suggests that disrupting lipid raft integrity or silencing caveolin-1, through several strategies including cholesterol-lowering molecules, can influence HER2 availability and internalization, enhancing anti-HER2 targeted therapy and offering a novel approach to counteract drug resistance and improve treatment efficacy.

Virus-like Particle (VLP) Vaccines for Cancer Immunotherapy.

Cancer vaccines are increasingly being studied as a possible strategy to prevent and treat cancers. While several prophylactic vaccines for virus-caused cancers are approved and efficiently used worldwide, the development of therapeutic cancer vaccines needs to be further implemented. Virus-like particles (VLPs) are self-assembled protein structures that mimic native viruses or bacteriophages but lack the replicative material. VLP platforms are designed to display single or multiple antigens with a high-density pattern, which can trigger both cellular and humoral responses. The aim of this review is to provide a comprehensive overview of preventive VLP-based vaccines currently approved worldwide against HBV and HPV infections or under evaluation to prevent virus-caused cancers. Furthermore, preclinical and early clinical data on prophylactic and therapeutic VLP-based cancer vaccines were summarized with a focus on HER-2-positive breast cancer.