Department of Cell Biology and Cancer Science, Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel.
European Centre for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Clin Exp Metastasis. 2024 Aug;41(4):495-507. doi: 10.1007/s10585-023-10243-5. Epub 2023 Nov 24.
Chemotherapy remains the primary treatment for most metastatic cancers. However, the response to chemotherapy and targeted agents is often transient, and concurrent development of resistance is the primary impediment to effective cancer therapy. Strategies to overcome resistance to treatment have focused on cancer cell intrinsic factors and the tumor microenvironment (TME). Recent evidence indicates that systemic chemotherapy has a significant impact on the host that either facilitates tumor growth, allowing metastatic spread, or renders treatment ineffective. These host responses include the release of bone marrow-derived cells, activation of stromal cells in the TME, and induction of different molecular effectors. Here, we provide an overview of chemotherapy-induced systemic host responses that support tumor aggressiveness and metastasis, and which contribute to therapy resistance. Studying host responses to chemotherapy provides a solid basis for the development of adjuvant strategies to improve treatment outcomes and delay resistance to chemotherapy. This review discusses the emerging field of host response to cancer therapy, and its preclinical and potential clinical implications, explaining how under certain circumstances, these host effects contribute to metastasis and resistance to chemotherapy.
化疗仍然是大多数转移性癌症的主要治疗方法。然而，化疗和靶向药物的反应往往是短暂的，同时产生耐药性是有效癌症治疗的主要障碍。克服耐药性的策略集中在癌细胞内在因素和肿瘤微环境（TME）上。最近的证据表明，全身化疗对宿主有显著影响，要么促进肿瘤生长，允许转移扩散，要么使治疗无效。这些宿主反应包括骨髓来源细胞的释放、TME 中基质细胞的激活以及不同分子效应物的诱导。在这里，我们概述了化疗引起的全身宿主反应，这些反应支持肿瘤侵袭性和转移，并导致治疗耐药性。研究宿主对化疗的反应为开发辅助策略提供了坚实的基础，以改善治疗效果并延迟对化疗的耐药性。本综述讨论了宿主对癌症治疗反应的新兴领域，及其临床前和潜在的临床意义，解释了在某些情况下，这些宿主效应如何促进转移和对化疗的耐药性。
