1 Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
2 Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Exp Biol Med (Maywood). 2018 Dec;243(17-18):1245-1255. doi: 10.1177/1535370218820287. Epub 2019 Jan 6.
Cancers kill mainly because metastatic disease is resistant to systemic therapies. It was hoped that newer targeted and immunomodulatory interventions could overcome these issues. However, recent findings point to a generalized resistance to elimination imparted by both cancer-intrinsic and -extrinsic changes to provide survival advantages to the disseminated tumor cells. Here, we present a novel conceptual framework for the microenvironmental inputs and changes that contribute to this generalized therapeutic resistance. In addition we address the issues of experimental systems in terms of studying this phenomenon with their advantages and limitations. This is meant to spur studies into this critical aspect of tumor progression that directly leads to cancer mortality.
癌症主要是由于转移性疾病对全身治疗具有耐药性而导致的。人们曾希望新的靶向和免疫调节干预措施能够克服这些问题。然而，最近的发现表明，由于肿瘤内在和外在的变化，普遍存在对消除的抵抗，从而为播散的肿瘤细胞提供生存优势。在这里，我们提出了一个新的概念框架，用于解释微环境输入和变化如何导致这种普遍的治疗抵抗。此外，我们还讨论了研究这种现象的实验系统的问题，包括其优缺点。这旨在激发对肿瘤进展这一关键方面的研究，因为这直接导致癌症的死亡率。
