bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–04–02
seven papers selected by
Muhammad Rizwan, COMSATS University



  1. Cancers (Basel). 2023 Mar 15. pii: 1776. [Epub ahead of print]15(6):
      Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients remains poor due to late diagnosis of the disease. This highlights the importance of early detection, wherein biomarker evaluation including exosomes would be helpful. Exosomes, small extracellular vesicles (sEVs), are cell-secreted entities with diameters ranging from 50 to 150 nm that deliver cellular contents (e.g., proteins, lipids, and nucleic acids) from parent cells to regulate the cellular processes of targeted cells. Recently, an increasing number of studies have reported that exosomes serve as messengers to facilitate stromal-immune crosstalk within the PDAC tumor microenvironment (TME), and their contents are indicative of disease progression. Moreover, evidence suggests that exosomes with specific surface markers are capable of distinguishing patients with PDAC from healthy individuals. Detectable exosomes in bodily fluids (e.g., blood, urine, saliva, and pancreatic juice) are omnipresent and may serve as promising biomarkers for improving early detection and evaluating patient prognosis. In this review, we shed light on the involvement of exosomes and their cargos in processes related to disease progression, including chemoresistance, angiogenesis, invasion, metastasis, and immunomodulation, and their potential as prognostic markers. Furthermore, we highlight feasible clinical applications and the limitations of exosomes in liquid biopsies as tools for early diagnosis as well as disease monitoring. Taking advantage of exosomes to improve diagnostic capacity may provide hope for PDAC patients, although further investigation is urgently needed.
    Keywords:  biomarker; exosome; pancreatic ductal adenocarcinoma; tumor microenvironment; tumor progression
    DOI:  https://doi.org/10.3390/cancers15061776
  2. Crit Rev Oncol Hematol. 2023 Mar 23. pii: S1040-8428(23)00055-0. [Epub ahead of print] 103967
      Cancer-associated fibroblasts (CAFs) are the prominent stromal cell population in the tumor microenvironment (TME), which play an indispensable role in cancer progression and response to therapy. CAFs provide communication between tumor cells and surrounding cells by secreting soluble biomolecules and extracellular vesicles (EVs). Exosomes are small membrane-bound EVs that contain various cargos, including growth factors, non-coding RNAs (ncRNAs), cytokines, and chemokines. These biomolecules can be transferred between cells within the TME and alter the behavior of recipient cells. Some studies have shown that exosomes secreted by CAFs contribute to resistance to chemotherapy and radiotherapy. This review focuses on CAF-derived exosomes in different types of tumors, with emphasis on resistance to chemotherapy and radiotherapy.
    Keywords:  Cancer-associated fibroblast; Chemotherapy resistance; Exosome; Radiation resistance; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.critrevonc.2023.103967
  3. Pharmaceuticals (Basel). 2023 Mar 10. pii: 421. [Epub ahead of print]16(3):
      Exosomes are cell-derived, nano-sized extracellular vesicles comprising a lipid bilayer membrane that encapsulates several biological components, such as nucleic acids, lipids, and proteins. The role of exosomes in cell-cell communication and cargo transport has made them promising candidates in drug delivery for an array of diseases. Despite several research and review papers describing the salient features of exosomes as nanocarriers for drug delivery, there are no FDA-approved commercial therapeutics based on exosomes. Several fundamental challenges, such as the large-scale production and reproducibility of batches, have hindered the bench-to-bedside translation of exosomes. In fact, compatibility and poor drug loading sabotage the possibility of delivering several drug molecules. This review provides an overview of the challenges and summarizes the potential solutions/approaches to facilitate the clinical development of exosomal nanocarriers.
    Keywords:  drug loading; exosomal delivery; exosome; large-scale production
    DOI:  https://doi.org/10.3390/ph16030421
  4. Biomolecules. 2023 03 01. pii: 456. [Epub ahead of print]13(3):
      Sarcoma is a heterogeneous group of mesenchymal neoplasms with a high rate of lung metastasis. The cellular mechanisms responsible for sarcoma metastasis remain poorly understood. Furthermore, there are limited efficacious therapeutic strategies for treating metastatic sarcoma. Improved diagnostic and therapeutic modalities are of increasing importance for the treatment of sarcoma due to their high mortality in the advanced stages of the disease. Recent evidence demonstrates that the exosome, a type of extracellular vesicle released by virtually all cells in the body, is an important facilitator of intercellular communication between the cells and the surrounding environment. The exosome is gaining significant attention among the medical research community, but there is little knowledge about how the exosome affects sarcoma metastasis. In this review, we summarize the multifaceted roles of sarcoma-derived exosomes in promoting the process of metastasis via the formation of pre-metastatic niche (PMN), the regulation of immunity, angiogenesis, vascular permeability, and the migration of sarcoma cells. We also highlight the potential of exosomes as innovative diagnostic and prognostic biomarkers as well as therapeutic targets in sarcoma metastasis.
    Keywords:  diagnostic biomarker; exosome; metastasis; sarcoma; therapeutic target
    DOI:  https://doi.org/10.3390/biom13030456
  5. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Feb 28. pii: 1672-7347(2023)02-0268-07. [Epub ahead of print]48(2): 268-274
      Pancreatic cancer (PC) is a malignant tumor of the digestive tract with poor patient prognosis. The PC incidence is still increasing with a 5-year survival rate of only 10%. At present, surgical resection is the most effective method to treat PC, however, 80% of the patients missed the best time for surgery after they have been diagnosed as PC. Chemotherapy is one of the main treating methods but PC is insensitive to chemotherapy, prone to drug resistance, and is accompanied by many side effects which are related to a lack of specific target. Exosomes are nanoscale vesicles secreted by almost all cell types and can carry various bioactive substances which mediate cell communication and material transport. They are characterized by a low immunogenicity, low cytotoxicity, high penetration potential and homing capacity, and possess the potential of being used as advanced drug carriers. Therefore, it is a hot research topic to use drug-loaded exosomes for tumor therapy. They may alleviate chemotherapy resistance, reduce side effects, and enhance the curative effect. In recent years, exosome drug carriers have achieved considerable results in PC chemotherapy studies.
    Keywords:  chemotherapy; drug carriers; drug resistance; exosomes; pancreatic cancer
    DOI:  https://doi.org/10.11817/j.issn.1672-7347.2023.220439
  6. Cancer Lett. 2023 Mar 29. pii: S0304-3835(23)00102-7. [Epub ahead of print] 216151
      Exosomes are natural extracellular nanovesicles (30-150 nm in diameter) with the ability to interact with and be taken up by specific cells. They are being explored as delivery systems and imaging agents for biomedical purposes owing to their biocompatibility, biostability in extracellular biofluids, and organotropic properties. However, their usefulness, efficacy, and clinical application are limited by certain critical parameters, including the need for more robust and reproducible manufacturing processes, characterization, quality control assessment, and clinical studies. Recently, exosome-like systems have emerged as alternatives for overcoming the limitations of natural exosomes. These systems are based on surface engineering approaches and nanoscale platforms that offer a deeper understanding and allow for more exhaustive standardization compared with natural exosomes. By combining the latest knowledge related to exosome research with the most promising developments in nanotechnology, exosome-like systems can be developed as a competitive approach for innovative targeted anti-cancer therapies. This review aims to provide a critical overview of the latest advances in designing and testing innovative exosome-like systems and the most promising modalities that can be translated into the clinic. Future perspectives and challenges in this field are discussed.
    Keywords:  Drug delivery; Engineered-exosomes; Exosome-mimetics; Liposomes; Nanomedicine
    DOI:  https://doi.org/10.1016/j.canlet.2023.216151
  7. Cancers (Basel). 2023 Mar 17. pii: 1826. [Epub ahead of print]15(6):
      Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many attempts have been made to improve the outcomes, but one of the bottlenecks is thought to be the lack of an effective biomarker with high sensitivity and specificity. Extracellular vesicles (EVs) are secreted by various cells and participate in a great number of intercellular communications. Based on liquid biopsy, EV detection in several biofluids, such as blood, saliva, and urine, has been applied to identify the existence and progression of a variety of cancers. In HNSCC, tumor-derived EVs exhibit many functionalities by transporting diverse cargoes, which highlights their importance in tumor screening, the determination of multidisciplinary therapy, prediction of prognosis, and evaluation of therapeutic effects. This review illustrates the classification and formation of EV subtypes, the cargoes conveyed by these vesicles, and their respective functions in HNSCC cancer biology, and discloses their potential as biomarkers during the whole process of tumor diagnosis, treatment, and follow-up.
    Keywords:  exosome; extracellular vesicles; head and neck squamous cell carcinoma; miRNA
    DOI:  https://doi.org/10.3390/cancers15061826