Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, The Netherlands.
Eur J Cancer. 2013 Jan;49(1):219-30. doi: 10.1016/j.ejca.2012.05.005. Epub 2012 Jun 9.
Classical chemotherapeutic anti-cancer treatments induce cell death through DNA damage by taking advantage of the proliferative behaviour of cancer cells. The more recent approach of targeted therapy (usually protein-targeted) has led to many treatments that are currently available or are under development, all of which are designed to strike at the critical driving forces of cancer cells. The interaction of the cancer cells with their microenvironment is one of these fundamental features of neoplasms that could be targeted in such cancer treatments. Haematological and solid tumour cells interact with their microenvironment through membrane chemokine receptors and their corresponding ligands, which are expressed in the tumour microenvironment. Important representatives of this system are the chemokine ligand CXCL12 and its receptor chemokine receptor 4 (CXCR4). This interaction can be disrupted by CXCR4 antagonists, and this concept is being used clinically to harvest haematopoietic stem/progenitor cells from bone marrow. CXCR4 and CXCL12 also have roles in tumour growth and metastasis, and more recently their roles in cancer cell-tumour microenvironment interaction and angiogenesis have been studied. Our review focuses on these roles and summarises strategies for treating cancer by disrupting this interaction with special emphasis on the CXCR4/CXCL12 axis. Finally, we discuss ongoing clinical trials with several classes of CXCR4 inhibitors, and their potential additive value for patients with a (therapy resistant) malignancy by sensitising cancer cells to conventional therapy.
经典的化疗抗癌治疗通过利用癌细胞的增殖行为来诱导细胞死亡，通过 DNA 损伤。最近的靶向治疗（通常是针对蛋白质的）方法已经导致了许多目前可用或正在开发的治疗方法，所有这些方法都是为了针对癌细胞的关键驱动因素。癌细胞与其微环境的相互作用是肿瘤的基本特征之一，可以在这些癌症治疗中靶向这种相互作用。血液肿瘤细胞和实体瘤细胞通过膜趋化因子受体及其在肿瘤微环境中表达的相应配体与微环境相互作用。该系统的重要代表是趋化因子配体 CXCL12 和其受体趋化因子受体 4（CXCR4）。这种相互作用可以被 CXCR4 拮抗剂破坏，这一概念正在临床上被用于从骨髓中采集造血干/祖细胞。CXCR4 和 CXCL12 也在肿瘤生长和转移中发挥作用，最近它们在癌细胞-肿瘤微环境相互作用和血管生成中的作用也得到了研究。我们的综述重点介绍了这些作用，并总结了通过破坏这种相互作用来治疗癌症的策略，特别强调了 CXCR4/CXCL12 轴。最后，我们讨论了正在进行的几种 CXCR4 抑制剂的临床试验，以及它们通过使癌细胞对常规治疗敏感而对（治疗耐药性）恶性肿瘤患者的潜在附加价值。
