Eulberg Dirk, Frömming Anna, Lapid Kfir, Mangasarian Aram, Barak Avital
TME Pharma AG, Berlin, Germany.
Front Oncol. 2022 Dec 8;12:1070243. doi: 10.3389/fonc.2022.1070243. eCollection 2022.
Multiple mechanisms promote tumor prosperity, which does not only depend on cell-autonomous, inherent abnormal characteristics of the malignant cells that facilitate rapid cell division and tumor expansion. The neoplastic tissue is embedded in a supportive and dynamic tumor microenvironment (TME) that nurtures and protects the malignant cells, maintaining and perpetuating malignant cell expansion. The TME consists of different elements, such as atypical vasculature, various innate and adaptive immune cells with immunosuppressive or pro-inflammatory properties, altered extracellular matrix (ECM), activated stromal cells, and a wide range of secreted/stroma-tethered bioactive molecules that contribute to malignancy, directly or indirectly. In this review, we describe the various TME components and provide examples of anti-cancer therapies and novel drugs under development that aim to target these components rather than the intrinsic processes within the malignant cells. Combinatory TME-modulating therapeutic strategies may be required to overcome the resistance to current treatment options and prevent tumor recurrence.
多种机制促进肿瘤的生长，肿瘤的生长不仅取决于癌细胞自身固有的异常特征，这些特征有助于细胞快速分裂和肿瘤扩张。肿瘤组织嵌入在一个支持性的动态肿瘤微环境（TME）中，该微环境滋养和保护恶性细胞，维持并使恶性细胞持续扩张。肿瘤微环境由不同的成分组成，如非典型血管、具有免疫抑制或促炎特性的各种先天和适应性免疫细胞、改变的细胞外基质（ECM）、活化的基质细胞，以及多种直接或间接促进恶性肿瘤的分泌/基质结合生物活性分子。在本综述中，我们描述了肿瘤微环境的各种组成成分，并列举了正在开发的旨在靶向这些成分而非恶性细胞内在过程的抗癌疗法和新型药物。可能需要联合调节肿瘤微环境的治疗策略来克服对当前治疗方案的耐药性并预防肿瘤复发。
