Novel therapeutic strategies targeting tumor-stromal interactions in pancreatic cancer.
Novel therapeutic strategies targeting tumor-stromal interactions in pancreatic cancer.
复制标题
针对胰腺癌肿瘤相互作用的新型治疗策略。
DOI：
10.3389/fphys.2013.00331
复制
发表时间：
2013
影响因子：
4
通讯作者：
Shimosegawa T
中科院分区：
文献类型：
--
作者：
Hamada S;Masamune A;Shimosegawa T
治疗抵抗和术后复发是胰腺癌预后不良的原因。传统疗法对控制胰腺癌的作用有限，导致肿瘤迅速重新生长。肿瘤-间质相互作用的不可或缺的作用，作为癌细胞的防御者并增强恶性潜力，现在正在被发现。例如，已经确定了诱导结缔组织增生的特定信号通路，例如声波刺猬（Shh）或结缔组织生长因子（CTGF），其抑制作用会导致结缔组织增生耗竭，并至少在胰腺癌小鼠体内模型中具有治疗优势。药物输送方法的革命导致了新型化疗方案的建立，提高了患者的生存率。此外，通过鉴定骨髓源性抑制细胞（MDSC）阐明了胰腺癌宿主的免疫抑制机制，该细胞也促进疾病进展。针对肿瘤基质的这些成分的策略在体外和体内揭示了某些抗癌作用，这表明基质靶向治疗的可能性。基质细胞功能的抑制增加了胰腺癌细胞对治疗干预的敏感性。进一步的研究将阐明肿瘤微环境的复杂性质，其靶向有可能改善临床结果。
Therapy-resistance and postoperative recurrence are causes of the poor prognosis in pancreatic cancer. Conventional therapies have a limited impact on the control of pancreatic cancer, resulting in the rapid re-growth of the tumor. The indispensable role of tumor-stromal interaction, which acts as a defender of cancer cells and enhances malignant potential, is being uncovered now. For example, specific signaling pathways for desmoplasia induction have been identified, such as sonic hedgehog (Shh) or connective tissue growth factor (CTGF), whose inhibition causes desmoplasia depletion and therapeutic advantages at least in in vivo mouse models of pancreatic cancer. Revolutions in drug delivery methods have led to the establishment of novel chemotherapeutic regimens, with better patient survival. Furthermore, mechanisms of immunosuppression in the pancreatic cancer-bearing host were clarified by the identification of myeloid-derived suppressor cells (MDSCs), which also promote disease progression. Strategies to target these components of the tumor stroma revealed certain anticancer effects in vitro and in vivo, suggesting the possibility of stroma-targeting therapy. Suppression of the stromal cell function increases the sensitivity of pancreatic cancer cells to therapeutic intervention. Further study will clarify the complex nature of the tumor microenvironment, the targeting of which has the potential to improve clinical outcome.
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影响因子：
24.5
作者：
Gao, R.;Brigstock, D. R.
通讯作者：
Brigstock, D. R.
影响因子：
24.5
作者：
Jacobetz MA;Chan DS;Neesse A;Bapiro TE;Cook N;Frese KK;Feig C;Nakagawa T;Caldwell ME;Zecchini HI;Lolkema MP;Jiang P;Kultti A;Thompson CB;Maneval DC;Jodrell DI;Frost GI;Shepard HM;Skepper JN;Tuveson DA
通讯作者：
Tuveson DA
影响因子：
29.4
作者：
Bachem, MG;Sch端nemann, M;Adler, G
通讯作者：
Adler, G
影响因子：
29.4
作者：
Erkan, Mert;Kleeff, Joerg;Friess, Helmut
通讯作者：
Friess, Helmut
影响因子：
50.3
作者：
Hingorani, SR;Wang, LF;Tuveson, DA
通讯作者：
Tuveson, DA