Materials-driven approaches to understand extrinsic drug resistance in cancer.
Materials-driven approaches to understand extrinsic drug resistance in cancer.
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作者：
转移性癌症的预后很差，因为它广泛扩散，并与内在和获得性耐药性有关。有效杀死耐药癌细胞的关键未满足的需求包括克服一些转移性癌症/病变的药物脱敏特征，以及针对肿瘤微环境和驻留癌细胞的遗传谱定制治疗方案。生物工程师和材料科学家正在开发技术，以确定转移部位如何排除治疗，以及转移部位的细胞外因子（包括细胞，蛋白质，代谢物，细胞外基质和非生物因子）如何显著影响药物药效学。两个迫在眉睫的挑战是确定来自肿瘤微环境的哪些特征或特征组合驱动耐药性，以及细胞外信号与内在细胞遗传学在确定药物反应方面的相对影响。复杂的系统生物学工具，可以去卷积拥挤的信号和反应网络，以及可控的微环境，能够提供离散和可调的细胞外线索，可以帮助我们开始询问高维度的相互作用，在病人的耐药性。
Metastatic cancer has a poor prognosis, because it is broadly disseminated and associated with both intrinsic and acquired drug resistance. Critical unmet needs in effectively killing drug resistant cancer cells include overcoming the drug desensitization characteristics of some metastatic cancers/lesions, and tailoring therapeutic regimens to both the tumor microenvironment and the genetic profiles of the resident cancer cells. Bioengineers and materials scientists are developing technologies to determine how metastatic sites exclude therapies, and how extracellular factors (including cells, proteins, metabolites, extracellular matrix, and abiotic factors) at metastatic sites significantly affect drug pharmacodynamics. Two looming challenges are determining which feature, or combination of features, from the tumor microenvironment drive drug resistance, and what the relative impact is of extracellular signals vs. intrinsic cell genetics in determining drug response. Sophisticated systems biology tools that can de-convolve a crowded network of signals and responses, as well as controllable microenvironments capable of providing discrete and tunable extracellular cues can help us begin to interrogate the high dimensional interactions governing drug resistance in patients.
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DOI：
10.1056/nejmoa1510016
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Choueiri TK;Escudier B;Powles T;Mainwaring PN;Rini BI;Donskov F;Hammers H;Hutson TE;Lee JL;Peltola K;Roth BJ;Bjarnason GA;Géczi L;Keam B;Maroto P;Heng DY;Schmidinger M;Kantoff PW;Borgman-Hagey A;Hessel C;Scheffold C;Schwab GM;Tannir NM;Motzer RJ;METEOR Investigators
通讯作者：
METEOR Investigators
DOI：
10.1073/pnas.2011342118
发表时间：
2021-01-19
影响因子：
11.1
作者：
Damaghi M;West J;Robertson-Tessi M;Xu L;Ferrall-Fairbanks MC;Stewart PA;Persi E;Fridley BL;Altrock PM;Gatenby RA;Sims PA;Anderson ARA;Gillies RJ
通讯作者：
Gillies RJ
癌症相关成纤维细胞靶向脂质体全面启动肿瘤微环境，与癌细胞靶向化疗药物递送系统联合治疗
影响因子：
10.8
作者：
Chen, Binlong;Dai, Wenbing;Zhang, Qiang
通讯作者：
Zhang, Qiang
影响因子：
22.7
作者：
Dai, Jinxiang;Cimino, Patrick J.;Gouin, Kenneth H. I. I. I. I. I. I.;Grzelak, Candice A.;Barrett, Alexander;Lim, Andrea R.;Long, Annalyssa;Weaver, Stephanie;Saldin, Lindsey T.;Uzamere, Aiyedun;Schulte, Vera;Clegg, Nigel;Pisarsky, Laura;Lyden, David;Bissell, Mina J.;Knott, Simon;Welm, Alana L.;Bielas, Jason H.;Hansen, Kirk C.;Winkler, Frank;Holland, Eric C.;Ghajar, Cyrus M.
通讯作者：
Ghajar, Cyrus M.
影响因子：
6.6
作者：
Barney, L. E.;Jansen, L. E.;Peyton, S. R.
通讯作者：
Peyton, S. R.