Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany.
Nat Rev Cancer. 2013 May;13(5):365-76. doi: 10.1038/nrc3498. Epub 2013 Mar 28.
Immunotherapies, signal transduction inhibitors and chemotherapies can successfully achieve remissions in advanced stage cancer patients, but durable responses are rare. Using malignant melanoma as a paradigm, we propose that therapy-induced injury to tumour tissue and the resultant inflammation can activate protective and regenerative responses that represent a shared resistance mechanism to different treatments. Inflammation-driven phenotypic plasticity alters the antigenic landscape of tumour cells, rewires oncogenic signalling networks, protects against cell death and reprogrammes immune cell functions. We propose that the successful combination of cancer treatments to tackle resistance requires an interdisciplinary understanding of these resistance mechanisms, supported by mathematical models.
免疫疗法、信号转导抑制剂和化疗可以成功地使晚期癌症患者缓解，但持久反应很少见。我们以恶性黑色素瘤为例，提出治疗引起的肿瘤组织损伤和随之而来的炎症可以激活保护性和再生性反应，这代表了对不同治疗的共同抵抗机制。炎症驱动的表型可塑性改变了肿瘤细胞的抗原景观，重新连接致癌信号网络，保护细胞免于死亡，并重新编程免疫细胞功能。我们提出，要成功地结合癌症治疗来解决耐药性问题，需要有数学模型支持的对这些耐药机制的跨学科理解。
