Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.

Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, tumor cells show various adaptive characteristics, such as changes in the expression of cancer hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) and more frequent cell communication. Because of the adaptation of cancer cells to hypoxia, exploring the association between cell communication mediators and hypoxia has become increasingly important. Exosomes are important information carriers in cell-to-cell communication. Abundant evidence has proven that hypoxia effects in the TME are mediated by exosomes, with the occasional formation of feedback loops. In this review, we equally focus on the biogenesis and heterogeneity of cancer-derived exosomes and their functions under hypoxia and describe the known and potential mechanism ascribed to exosomes and hypoxia. Notably, we call attention to the size change of hypoxic cancer cell-derived exosomes, a characteristic long neglected, and propose some possible effects of this size change. Finally, jointly considering recent developments in the understanding of exosomes and tumors, we describe noteworthy problems in this field that urgently need to be solved for better research and clinical application.

Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.