Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer

Abstract

Mounting evidence indicates that tumor-derived exosomes (TDEs) play critical roles in tumor development and progression by regulating components in the tumor microenvironment (TME) in an autocrine or paracrine manner. Moreover, due to their delivery of critical molecules that react to chemotherapy and immunotherapy, TDEs also contribute to tumor drug resistance and impede the effective response of antitumor immunotherapy, thereby leading to poor clinical outcomes. There is a pressing need for the inhibition or removal of TDEs to facilitate the treatment and prognosis of cancer patients. Here, in the present review, we systematically overviewed the current strategies for TDE inhibition and clearance, providing novel insights for future tumor interventions in translational medicine. Moreover, existing challenges and potential prospects for TDE-targeted cancer therapy are also discussed to bridge the gaps between progress and promising applications.

The effects of MYC on exosomes derived from cancer cells in the context of breast cancer

“…These results suggested that cellular MYC can regulates keystones of the tumor environment by potentially shifting exosomal content in breast cancer. Consistent with our findings, Kilinc et al reported that oncogene MYC alters RNA and protein composition of small extracellular vesicles secreted from cells (Kilinc et al, 2021; Li et al, 2022). Exosomes are increasingly challenging as important mediators of intercellular communication that play roles in the different steps of cancer.…”

The role of lipid metabolic reprogramming in tumor microenvironment

“…For example, exosomes secreted by APCs can stimulate the proliferation of T cells 42 . Exosomes derived from M2 macrophages can transfer key enzymes of the PG pathway to tumor cells, such as cyclo-oxygenase 1 (COX1) and TXA synthase 1 43 . Therefore, exosomes have great potential in tumor therapy including immunotherapy.…”

Co-Delivery of Hesperetin and Cisplatin via Hyaluronic Acid-Modified Liposome for Targeted Inhibition of Aggression and Metastasis of Triple-Negative Breast Cancer

“…Therefore, disruption and inhibition of the tumor inflammatory microenvironment as well as deeper tumor penetration seem to be promising strategies to eradicate the entire solid tumor for suppressing metastasis. 3 In the present study, the CDDP cross-linked HA in the outer layer not only is for the targeted co-delivery of CDDP and Hes entrapped liposomes but also exhibits anti-inflammatory effects. Liposome with a tunable size and versatile modification surface is widely used as a carrier of anti-cancer drugs, which can enhance penetration and accumulation of traditional chemotherapeutic drugs at tumor sites through the enhanced permeability and retention (EPR) effect and active targeting.…”

“…Canonically, the tumor inflammatory microenvironment may contribute to a heterogeneous circumstance, which make chemotherapeutic drugs only to kill cancer cells at or near the periphery but not reach the interior area of the solid tumor, and to some extent, it can be used to explain the drug sensitivity decrease in CDDP treatment. Therefore, disruption and inhibition of the tumor inflammatory microenvironment as well as deeper tumor penetration seem to be promising strategies to eradicate the entire solid tumor for suppressing metastasis …”

“…Importantly, it is more biologically aggressive to early recurrence and distant metastasis. Metastasis to important organs including lung and brain accounts for more than 90% of mortality in clinic . For the occurrence of pulmonary metastasis, cancer cells are thought to undergo several steps, including invasion into surrounding tissues and the circulatory system, transporting to lung tissues through vascularization and colonization in lungs. , Not able to respond to hormone therapy and trastuzumab makes TNBC have higher mortality than other subtypes of breast cancers.…”