ABSTRACT
Immunotherapy is now a mainstay in cancer treatments. Programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) therapies have opened up a new venue of advanced cancer immunotherapy. However, hyperprogressive disease (HPD) induced by PD-1/PD-L1 inhibitors caused a significant decrease in the overall survival (OS) of the patients, which compromise the efficacy of PD-1/PD-L1 inhibitors. Therefore, HPD has become an urgent issue to be addressed in the clinical uses of PD-1/PD-L1 inhibitors. The mechanisms of HPD remain unclear, and possible predictive factors of HPD are not well understood. In this review, we summarized the potential mechanisms of HPD and coping strategies that can effectively reduce the occurrence and development of HPD.
Subject(s)
Immune Checkpoint Inhibitors , Programmed Cell Death 1 Receptor , Adaptation, Psychological , Disease Progression , Humans , Immune Checkpoint Inhibitors/therapeutic use , ImmunotherapyABSTRACT
Exosomes derived from tumor cells contain various molecular components, such as proteins, RNA, DNA, lipids, and carbohydrates. These components play a crucial role in all stages of tumorigenesis and development. Moreover, they reflect the physiological and pathological status of parental tumor cells. Recently, tumor-derived exosomes have become popular biomarkers for non-invasive liquid biopsy and the diagnosis of numerous cancers. The interdisciplinary significance of exosomes research has also attracted growing enthusiasm. However, the intrinsic nature of tumor-derived exosomes requires advanced methods to detect and evaluate the complex biofluid. This review analyzes the relationship between exosomes and tumors. It also summarizes the exosomal biological origin, composition, and application of molecular markers in clinical cancer diagnosis. Remarkably, this paper constitutes a comprehensive summary of the innovative research on numerous detection strategies for tumor-derived exosomes with the intent of providing a theoretical basis and reference for early diagnosis and clinical treatment of cancer.
Subject(s)
Biomarkers, Tumor , Exosomes/metabolism , Neoplasms/diagnosis , Neoplasms/metabolism , Cell-Free Nucleic Acids , Circulating Tumor DNA , Disease Susceptibility , Early Detection of Cancer/methods , Humans , Liquid Biopsy/methods , Molecular Diagnostic Techniques , Neoplasms/etiology , Oncogene Proteins , SELEX Aptamer Technique , Spectrum Analysis, Raman/methodsABSTRACT
Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene reverses tumor resistance include inhibiting the efflux of ATP binding cassette subfamily B member 1(ABCB1) transporter, reducing the transmission of exosomes, inducing apoptosis and autophagy, regulating the expression of key genes and proteins in various signaling pathways, blocking the cell cycle, inhibiting stemness, epithelial-mesenchymal transition, and so on. In this paper, the mechanisms of elemene's reversal of drug resistance are comprehensively reviewed.
Subject(s)
Drug Resistance, Neoplasm/drug effects , Neoplasms/drug therapy , Sesquiterpenes/pharmacology , Antineoplastic Agents/therapeutic use , Autophagy , Cell Line, Tumor , Cell Survival/drug effects , Drug Synergism , Exosomes/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neoplasms/metabolism , Sesquiterpenes/therapeutic useABSTRACT
Extracellular vesicles (EVs), are membrane-bound vesicles that have many advantages over traditional nanocarriers for drug and gene delivery. Evidence from recent studies indicate that EVs have therapeutic capability with chemical or biological modification. Tumor-derived exosomes (TEXs) were used as a new type of antigens or tumor vaccines in anti-tumor immunotherapy. With superior characteristics, modified EVs were applied to loaded and delivered synthetic drugs, silencing RNA, and microRNA for treatment. Different surface functionalization strategies have been proposed to improve the therapeutic functions of EVs. Appropriately modified EVs for disease intervention provide new avenues for effective clinical treatment strategies. Therefore, this review aimed at elucidating the therapeutic functions of EVs to generate new ideas for treatment and to unlock their hidden potential in translational medicine.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Delivery Systems , Exosomes/chemistry , Extracellular Vesicles/chemistry , Neoplasms/therapy , Antineoplastic Agents/chemistry , Cancer Vaccines/chemistry , Cancer Vaccines/therapeutic use , Genetic Therapy/methods , Humans , Translational Science, BiomedicalABSTRACT
Exosomes carry genetic information originating from their parental cells, raising their possibility as novel noninvasive biomarkers for cancer. Tumor-derived exosomes (TEXs) have a variety of endogenous cargos that reflect the pathophysiology status and information of tumor cells. TEXs are increasingly being recognized as potential biomarkers for cancer diagnosis prognosis, and monitoring. It is important to develop a variety of sensitive methods, including probes and biomaterials to isolate exosomes. A variety of approaches for detecting exosomes have been established. By combining exosome DNA and RNA sequencing tools, exosome proteomics analysis and immunoassay technology, it is expected that exosomes will gain widespread use in the diagnosis and treatment of cancer.
