Law Zhu-Jun, Khoo Xin Hui, Lim Pei Tee, Goh Bey Hing, Ming Long Chiau, Lee Wai-Leng, Goh Hui Poh
School of Science, Monash University Malaysia, Selangor, Malaysia.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Front Mol Biosci. 2021 Mar 9;8:629888. doi: 10.3389/fmolb.2021.629888. eCollection 2021.
Oral Squamous Cell Carcinoma (OSCC) remains a cancer with poor prognosis and high recurrence rate. Even with multimodal treatment options available for OSCC, tumor drug resistance is still a persistent problem, leading to increased tumor invasiveness among OSCC patients. An emerging trend of thought proposes that extracellular vesicles (EVs) play a role in facilitating tumor progression and chemoresistance via signaling between tumor cells. In particular, exosomes and microvesicles are heavily implicated in this process by various studies. Where primary studies into a particular EV-mediated chemoresistance mechanism in OSCC are limited, similar studies on other cancer cell types will be used in the discussion below to provide ideas for a new line of investigation into OSCC chemoresistance. By understanding how EVs are or may be involved in OSCC chemoresistance, novel targeted therapies such as EV inhibition may be an effective alternative to current treatment options in the near future. In this review, the current understandings on OSCC drug mechanisms under the novel context of exosomes and microvesicles were reviewed, including shuttling of miRNA content, drug efflux, alteration of vesicular pH, anti-apoptotic signaling, modulation of DNA damage repair, immunomodulation, epithelial-to-mesenchymal transition and maintenance of tumor by cancer stem cells.
口腔鳞状细胞癌（OSCC）仍然是一种预后较差且复发率高的癌症。即使有多种针对OSCC的多模式治疗方案，肿瘤耐药性仍然是一个持续存在的问题，导致OSCC患者的肿瘤侵袭性增加。一种新出现的观点认为，细胞外囊泡（EVs）通过肿瘤细胞之间的信号传导在促进肿瘤进展和化疗耐药性方面发挥作用。特别是，各种研究都强烈表明外泌体和微囊泡参与了这一过程。由于对OSCC中特定的EV介导的化疗耐药机制的初步研究有限，下面将讨论对其他癌细胞类型的类似研究，为OSCC化疗耐药性的新研究方向提供思路。通过了解EVs如何或可能参与OSCC化疗耐药性，诸如抑制EVs等新型靶向治疗在不久的将来可能成为当前治疗方案的有效替代方法。在这篇综述中，我们回顾了在外泌体和微囊泡这一新背景下对OSCC药物机制的当前认识，包括miRNA含量的穿梭、药物外排、囊泡pH值的改变、抗凋亡信号传导、DNA损伤修复的调节、免疫调节、上皮-间质转化以及癌症干细胞对肿瘤的维持作用。
