Advances in Pancreatic Ductal Adenocarcinoma Treatment.
Advances in Pancreatic Ductal Adenocarcinoma Treatment.
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DOI：
10.3390/cancers13215510
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发表时间：
2021-11-03
期刊：
影响因子：
5.2
通讯作者：
Osipov A
中科院分区：
文献类型：
--
作者：
Anderson EM;Thomassian S;Gong J;Hendifar A;Osipov A
胰腺癌仍然是用标准方法治疗最具挑战性的恶性肿瘤之一。新出现的治疗方法结合了创新的外科技术和新的系统疗法，可能有助于改善胰腺癌患者的预后。尽管与免疫原性较高的肿瘤类型相比，免疫疗法对胰腺癌的治疗效果较差，但目前正在积极研究多种免疫系统刺激剂对胰腺癌的治疗，无论是单独使用还是与其他治疗药物联合使用。胰腺癌的肿瘤微环境也是一个有吸引力的治疗靶点，因为它被认为是高度免疫抑制的，并被致密的间质包裹。这篇综述文章旨在总结临床前和临床研究，包括正在进行的临床试验，这些试验试图纳入胰腺癌的新治疗方法。新出现的治疗方法可能有助于显著改善这种难以治疗的疾病的结果。胰腺导管腺癌(PDAC)是所有癌症中死亡率最高的恶性肿瘤之一。尽管治疗意图、手术和使用标准的细胞毒化疗和放射治疗，PDAC仍然对治疗耐药。近年来，更现代的治疗方法，如通过检查点抑制进行免疫治疗，已经在许多其他恶性肿瘤中显示出一些希望，但PDAC仍然缺乏有效的根治疗法。在研究这些现象时，研究表明，PDAC显著的促结缔组织增生性和适应性肿瘤微环境(TME)促进了免疫抑制细胞的增殖，并成为治疗效果的主要障碍。在这篇综述中，我们探讨了与PDAC治疗相关的挑战，包括其独特的免疫抑制TME。本文综述了外科手术在PDAC中的作用，外科手术入路的最新进展和外科手术的优化。我们进一步关注免疫治疗方法的进展，包括检查点抑制、CD40激动剂，并讨论了未来基于免疫的有前景的策略，例如治疗性新抗原癌症疫苗，作为克服PDAC密集的间质和免疫环境下的耐药机制的手段。我们还通过针对KRAS、FAK、CCR2/CCR5、CXCR4、PARP和癌症相关成纤维细胞的新型小分子抑制剂来探索独特的信号、TME和基质靶向。这篇综述还通过回顾克服PDAC治疗难治性的当代联合治疗方法，探索了在胰腺癌治疗中最有前途的策略。
Pancreatic cancer remains one of the most challenging malignancies to treat with standard approaches. Emerging treatment approaches incorporating innovative surgical techniques and novel systemic therapies may help to improve outcomes for pancreas cancer patients. Although immunotherapy has proven to be less effective for the treatment of pancreas cancer relative to more immunogenic tumor types, multiple immune system stimulating agents are under active investigation for pancreatic ductal adenocarcinoma, either alone or in combination with other therapeutic agents. The tumor microenvironment of pancreatic cancer is also an attractive therapeutic target given that it is believed to be highly immunosuppressive and encapsulated by a dense stroma. This review article aims to summarize pre-clinical and clinical studies, including ongoing clinical trials, which attempt to incorporate novel treatment approaches for pancreas cancer. Emerging treatment approaches may help to significantly improve outcomes for this tough to treat disease. Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest malignancies among all cancers. Despite curative intent, surgery and the use of standard cytotoxic chemotherapy and radiation therapy, PDAC remains treatment-resistant. In recent years, more contemporary treatment modalities such as immunotherapy via checkpoint inhibition have shown some promise in many other malignancies, yet PDAC still eludes an effective curative treatment. In investigating these phenomena, research has suggested that the significant desmoplastic and adaptive tumor microenvironment (TME) of PDAC promote the proliferation of immunosuppressive cells and act as major obstacles to treatment efficacy. In this review, we explore challenges associated with the treatment of PDAC, including its unique immunosuppressive TME. This review examines the role of surgery in PDAC, recent advances in surgical approaches and surgical optimization. We further focus on advances in immunotherapeutic approaches, including checkpoint inhibition, CD40 agonists, and discuss promising immune-based future strategies, such as therapeutic neoantigen cancer vaccines as means of overcoming the resistance mechanisms which underly the dense stroma and immune milieu of PDAC. We also explore unique signaling, TME and stromal targeting via novel small molecule inhibitors, which target KRAS, FAK, CCR2/CCR5, CXCR4, PARP and cancer-associated fibroblasts. This review also explores the most promising strategy for advancement in treatment of pancreatic cancer by reviewing contemporary combinatorial approaches in efforts to overcome the treatment refractory nature of PDAC.
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DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.
DOI：
10.1084/jem.188.10.1849
发表时间：
1998-11-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen W;Jin W;Wahl SM
通讯作者：
Wahl SM
影响因子：
3.2
作者：
Digiacomo, Graziana;Tusa, Ignazia;Rovida, Elisabetta
通讯作者：
Rovida, Elisabetta
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
DOI：
10.1073/pnas.0406035101
发表时间：
2004-09-21
影响因子：
11.1
作者：
Brockstedt, DG;Giedlin, MA;Dubensky, TW
通讯作者：
Dubensky, TW