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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

血管生成和胰腺癌:克服治疗耐药性的新方法

卷 24, 期 11, 2024

发表于: 31 January, 2024

页: [1116 - 1127] 页: 12

弟呕挨: 10.2174/0115680096284588240105051402

价格: $65

摘要

胰腺癌(PCa)被认为是全球癌症相关死亡率的重要贡献者,被广泛认为是最具挑战性的恶性疾病之一。胰腺导管腺癌(PDAC)是最常见的前列腺癌类型,具有高度侵袭性,大多数无法治愈。血管生成分子的普遍存在加剧了这种肿瘤的不良预后,血管生成分子有助于基质僵硬和免疫逃逸。PDAC过表达多种促血管生成蛋白,包括血管内皮生长因子(VEGF)-A,这些分子的水平与预后不良和治疗抵抗相关。此外,以vegf为靶点的抗血管生成治疗与缺氧引起的抵抗的发生有关,而缺氧反过来又诱导血管生成分子的产生。此外,过度的血管生成是第二种最常见的前列腺癌的特征之一,即胰腺神经内分泌肿瘤(PNET)。在这篇综述中,血管生成调节剂在促进前列腺癌疾病进展中的作用,以及这些分子对吉西他滨和各种前列腺癌治疗的耐药性的影响进行了讨论。最后,本文讨论了抗血管生成药物与化疗和其他靶向治疗分子的联合使用,作为克服当前PCa治疗局限性的新解决方案。

关键词: 胰腺导管腺癌,血管生成调节剂,免疫治疗,缺氧,胰腺神经内分泌肿瘤,免疫检查点抑制剂。

图形摘要
[1]
Mittal, D.; Gubin, M.M.; Schreiber, R.D.; Smyth, M.J. New insights into cancer immunoediting and its three component phases—elimination, equilibrium and escape. Curr. Opin. Immunol., 2014, 27, 16-25.
[http://dx.doi.org/10.1016/j.coi.2014.01.004] [PMID: 24531241]
[2]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2021. Cancer J Clin, 2021, 71(1), 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[3]
Mizrahi, J.D.; Surana, R.; Valle, J.W.; Shroff, R.T. Pancreatic cancer. Lancet, 2020, 395(10242), 2008-2020.
[http://dx.doi.org/10.1016/S0140-6736(20)30974-0] [PMID: 32593337]
[4]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin, 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[5]
McGuigan, A.; Kelly, P.; Turkington, R.C.; Jones, C.; Coleman, H.G.; McCain, R.S. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J. Gastroenterol., 2018, 24(43), 4846.
[http://dx.doi.org/10.3748/wjg.v24.i43.4846] [PMID: 30487695]
[6]
Kamisawa, T.; Wood, L.D.; Itoi, T.; Takaori, K. Pancreatic cancer. Lancet, 2016, 388(10039), 73-85.
[http://dx.doi.org/10.1016/S0140-6736(16)00141-0] [PMID: 26830752]
[7]
Annese, T.; Tamma, R.; Ruggieri, S.; Ribatti, D. Angiogenesis in pancreatic cancer: Pre-clinical and clinical studies. Cancers, 2019, 11(3), 381.
[http://dx.doi.org/10.3390/cancers11030381] [PMID: 30889903]
[8]
Tamburrino, A.; Piro, G.; Carbone, C.; Tortora, G.; Melisi, D. Mechanisms of resistance to chemotherapeutic and anti-angiogenic drugs as novel targets for pancreatic cancer therapy. Front. Pharmacol., 2013, 4, 56.
[http://dx.doi.org/10.3389/fphar.2013.00056] [PMID: 23641216]
[9]
Mabeta, P.; Pepper, M.S. A comparative study on the anti-angiogenic effects of DNA-damaging and cytoskeletal-disrupting agents. Angiogenesis, 2009, 12, 81-90.
[http://dx.doi.org/10.1007/s10456-009-9134-8] [PMID: 19214765]
[10]
Mabeta, P.; Hull, R.; Dlamini, Z. LncRNAs and the angiogenic switch in cancer: Clinical significance and therapeutic opportunities. Genes, 2022, 13(1), 152.
[http://dx.doi.org/10.3390/genes13010152] [PMID: 35052495]
[11]
Ma, S.; Pradeep, S.; Hu, W.; Zhang, D.; Coleman, R.; Sood, A. The role of tumor microenvironment in resistance to anti-angiogenic therapy. F1000 Res., 2018, 7.
[http://dx.doi.org/10.12688/f1000research.11771.1] [PMID: 29560266]
[12]
Itakura, J.; Ishiwata, T.; Friess, H.; Fujii, H.; Matsumoto, Y.; Büchler, M.; Korc, M. Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clin Cancer Res: Am J Cancer Res, 1997, 3(8), 1309-1316.
[PMID: 9815813]
[13]
Ikeda, N.; Adachi, M.; Taki, T.; Huang, C.; Hashida, H.; Takabayashi, A.; Sho, M.; Nakajima, Y.; Kanehiro, H.; Hisanaga, M. Prognostic significance of angiogenesis in human pancreatic cancer. Br. J. Cancer, 1999, 79(9), 1553-1563.
[http://dx.doi.org/10.1038/sj.bjc.6690248] [PMID: 10188906]
[14]
Morin, E.; Sjöberg, E.; Tjomsland, V.; Testini, C.; Lindskog, C.; Franklin, O.; Sund, M.; Öhlund, D.; Kiflemariam, S.; Sjöblom, T. VEGF receptor-2/neuropilin 1 trans-complex formation between endothelial and tumor cells is an independent predictor of pancreatic cancer survival. J. Pathol., 2018, 246(3), 311-322.
[http://dx.doi.org/10.1002/path.5141] [PMID: 30027561]
[15]
Kuwahara, K.; Sasaki, T.; Kuwada, Y.; Murakami, M.; Yamasaki, S.; Chayama, K. Expressions of angiogenic factors in pancreatic ductal carcinoma: A correlative study with clinicopathologic parameters and patient survival. Pancreas, 2003, 26(4), 344-349.
[http://dx.doi.org/10.1097/00006676-200305000-00006] [PMID: 12717266]
[16]
Hoffmann, A-C.; Mori, R.; Vallbohmer, D.; Brabender, J.; Klein, E.; Drebber, U.; Baldus, S.E.; Cooc, J.; Azuma, M.; Metzger, R. High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF. Neoplasia, 2008, 10(7), 674-679.
[http://dx.doi.org/10.1593/neo.08292] [PMID: 18592007]
[17]
Lee, J.; Lee, J.; Yun, J.H.; Choi, C.; Cho, S.; Kim, S.J.; Kim, J.H. Autocrine DUSP28 signaling mediates pancreatic cancer malignancy via regulation of PDGF-A. Sci. Rep., 2017, 7(1), 12760.
[http://dx.doi.org/10.1038/s41598-017-13023-w] [PMID: 28986588]
[18]
Zahra, F.T.; Sajib, M.S.; Mikelis, C.M. Role of bFGF in acquired resistance upon anti-VEGF therapy in cancer. Cancers, 2021, 13(6), 1422.
[http://dx.doi.org/10.3390/cancers13061422] [PMID: 33804681]
[19]
Pavel, M.E.; Hassler, G.; Baum, U.; Hahn, E.G.; Lohmann, T.; Schuppan, D. Circulating levels of angiogenic cytokines can predict tumour progression and prognosis in neuroendocrine carcinomas. Clin. Endocrinol., 2005, 62(4), 434-443.
[http://dx.doi.org/10.1111/j.1365-2265.2005.02238.x] [PMID: 15807874]
[20]
Inman, K.S.; Francis, A.A.; Murray, N.R. Complex role for the immune system in initiation and progression of pancreatic cancer. World J. Gastroenterol., 2014, 20(32), 11160-11181.
[http://dx.doi.org/10.3748/wjg.v20.i32.11160] [PMID: 25170202]
[21]
Dunn, G.P.; Bruce, A.T.; Ikeda, H.; Old, L.J.; Schreiber, R.D. Cancer immunoediting: From immunosurveillance to tumor escape. Nat. Immunol., 2002, 3(11), 991-998.
[http://dx.doi.org/10.1038/ni1102-991] [PMID: 12407406]
[22]
Arum, C-J.; Anderssen, E.; Viset, T.; Kodama, Y.; Lundgren, S.; Chen, D.; Zhao, C-M. Cancer immunoediting from immunosurveillance to tumor escape in microvillus-formed niche: A study of syngeneic orthotopic rat bladder cancer model in comparison with human bladder cancer. Neoplasia, 2010, 12(6), 434-442.
[http://dx.doi.org/10.1593/neo.91824] [PMID: 20563246]
[23]
O’Donnell, J.S.; Teng, M.W.; Smyth, M.J. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat. Rev. Clin. Oncol., 2019, 16(3), 151-167.
[http://dx.doi.org/10.1038/s41571-018-0142-8] [PMID: 30523282]
[24]
Fukumura, D.; Kloepper, J.; Amoozgar, Z.; Duda, D.G.; Jain, R.K. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat. Rev. Clin. Oncol., 2018, 15(5), 325-340.
[http://dx.doi.org/10.1038/nrclinonc.2018.29] [PMID: 29508855]
[25]
Riboldi, E.; Musso, T.; Moroni, E.; Urbinati, C.; Bernasconi, S.; Rusnati, M.; Adorini, L.; Presta, M.; Sozzani, S. Cutting edge: Proangiogenic properties of alternatively activated dendritic cells. J. Immun., 2005, 175(5), 2788-2792.
[http://dx.doi.org/10.4049/jimmunol.175.5.2788] [PMID: 16116163]
[26]
Li, Y-L.; Zhao, H.; Ren, X-B. Relationship of VEGF/VEGFR with immune and cancer cells: Staggering or forward? Cancer Biol. Med., 2016, 13(2), 206.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2015.0070] [PMID: 27458528]
[27]
Esposito, I.; Menicagli, M.; Funel, N.; Bergmann, F.; Boggi, U.; Mosca, F.; Bevilacqua, G.; Campani, D. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J. Clin. Pathol., 2004, 57(6), 630-636.
[http://dx.doi.org/10.1136/jcp.2003.014498] [PMID: 15166270]
[28]
Petrova, V.; Annicchiarico-Petruzzelli, M.; Melino, G.; Amelio, I. The hypoxic tumour microenvironment. Oncogenesis, 2018, 7(1), 10.
[http://dx.doi.org/10.1038/s41389-017-0011-9] [PMID: 29362402]
[29]
Tao, J.; Yang, G.; Zhou, W.; Qiu, J.; Chen, G.; Luo, W.; Zhao, F.; You, L.; Zheng, L.; Zhang, T. Targeting hypoxic tumor microenvironment in pancreatic cancer. J. Hematol. Oncol., 2021, 14, 1-25.
[http://dx.doi.org/10.1186/s13045-020-01030-w] [PMID: 33436044]
[30]
Muz, B.; de la Puente, P.; Azab, F.; Kareem Azab, A. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia, 2015, 83-92.
[http://dx.doi.org/10.2147/HP.S93413] [PMID: 27774485]
[31]
Hao, J. HIF-1 is a critical target of pancreatic cancer. OncoImmunology, 2015, 4(9), e1026535.
[http://dx.doi.org/10.1080/2162402X.2015.1026535] [PMID: 26405594]
[32]
Fuentes, N.R.; Phan, J.; Huang, Y.; Lin, D.; Taniguchi, C.M. Resolving the HIF paradox in pancreatic cancer. Cancer Lett., 2020, 489, 50-55.
[http://dx.doi.org/10.1016/j.canlet.2020.05.033] [PMID: 32512024]
[33]
Garvalov, B.K.; Acker, T. Implications of oxygen homeostasis for tumor biology and treatment. Hypoxia, 2016, 169-185.
[http://dx.doi.org/10.1007/978-1-4899-7678-9_12] [PMID: 27343096]
[34]
Unger, K.; Mehta, K.Y.; Kaur, P.; Wang, Y.; Menon, S.S.; Jain, S.K.; Moonjelly, R.A.; Suman, S.; Datta, K.; Singh, R. Metabolomics based predictive classifier for early detection of pancreatic ductal adenocarcinoma. Oncotarget, 2018, 9(33), 23078-23090.
[http://dx.doi.org/10.18632/oncotarget.25212] [PMID: 29796173]
[35]
Canto, M.I.; Harinck, F.; Hruban, R.H.; Offerhaus, G.J.; Poley, J-W.; Kamel, I.; Nio, Y.; Schulick, R.S.; Bassi, C.; Kluijt, I. International cancer of the pancreas screening (CAPS) consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut, 2013, 62(3), 339-347.
[http://dx.doi.org/10.1136/gutjnl-2012-303108] [PMID: 23135763]
[36]
Henrikson, N.B.; Bowles, E.J.A.; Blasi, P.R.; Morrison, C.C.; Nguyen, M.; Pillarisetty, V.G.; Lin, J.S. Screening for pancreatic cancer: Updated evidence report and systematic review for the us preventive services task force. JAMA, 2019, 322(5), 445-454.
[http://dx.doi.org/10.1001/jama.2019.6190] [PMID: 31386140]
[37]
van Manen, L.; Groen, J.V.; Putter, H.; Vahrmeijer, A.L.; Swijnenburg, R-J.; Bonsing, B.A.; Mieog, J.S.D. Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis. Biomarkers, 2020, 25(2), 186-193.
[http://dx.doi.org/10.1080/1354750X.2020.1725786] [PMID: 32009482]
[38]
Meng, Q.; Shi, S.; Liang, C.; Xiang, J.; Liang, D.; Zhang, B.; Qin, Y.; Ji, S.; Xu, W.; Xu, J. Diagnostic accuracy of a CA125-based biomarker panel in patients with pancreatic cancer: A systematic review and meta-analysis. J. Cancer, 2017, 8(17), 3615-3622.
[http://dx.doi.org/10.7150/jca.18901] [PMID: 29151947]
[39]
Cai, J.; Chen, H.; Lu, M.; Zhang, Y.; Lu, B.; You, L.; Zhang, T.; Dai, M.; Zhao, Y. Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis. Cancer Lett., 2021, 520, 1-11.
[http://dx.doi.org/10.1016/j.canlet.2021.06.027] [PMID: 34216688]
[40]
Chun, Y.S.; Pawlik, T.M.; Vauthey, J-N. Of the AJCC cancer staging manual: Pancreas and hepatobiliary cancers. Ann. Surg. Oncol., 2018, 25, 845-847.
[http://dx.doi.org/10.1245/s10434-017-6025-x] [PMID: 28752469]
[41]
Board, P.A.T.E. Pancreatic cancer treatment (PDQ®). PDQ cancer information summaries; National Cancer Institute: US, 2023.
[42]
Hidalgo, M. Pancreatic cancer. N. Engl. J. Med., 2010, 362(17), 1605-1617.
[http://dx.doi.org/10.1056/NEJMra0901557] [PMID: 20427809]
[43]
Crane, C.H.; Winter, K.; Regine, W.F.; Safran, H.; Rich, T.A.; Curran, W.; Wolff, R.A.; Willett, C.G. Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation therapy oncology group RTOG 0411. J. Clin. Oncol., 2009, 27(25), 4096-4102.
[http://dx.doi.org/10.1200/JCO.2009.21.8529] [PMID: 19636002]
[44]
Koukourakis, M.I.; Giatromanolaki, A., II; Sheldon, H.; Buffa, F.M.; Kouklakis, G.; Ragoussis, I.; Sivridis, E.; Harris, A.L. Tumour; Group, A.R. Phase I/II trial of bevacizumab and radiotherapy for locally advanced inoperable colorectal cancer: Vasculature-independent radiosensitizing effect of bevacizumab. Clin. Cancer Res., 2009, 15(22), 7069-7076.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0688] [PMID: 19887481]
[45]
Kindler, H.L.; Friberg, G.; Singh, D.A.; Locker, G.; Nattam, S.; Kozloff, M.; Taber, D.A.; Karrison, T.; Dachman, A.; Stadler, W.M. Phase trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J. Clin. Oncol., 2005, 23(31), 8033-8040.
[http://dx.doi.org/10.1200/JCO.2005.01.9661] [PMID: 16258101]
[46]
Spano, J-P.; Chodkiewicz, C.; Maurel, J.; Wong, R.; Wasan, H.; Barone, C.; Létourneau, R.; Bajetta, E.; Pithavala, Y.; Bycott, P. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: An open-label randomised phase II study. Lancet, 2008, 371(9630), 2101-2108.
[http://dx.doi.org/10.1016/S0140-6736(08)60661-3] [PMID: 18514303]
[47]
Kindler, H.L.; Ioka, T.; Richel, D.J.; Bennouna, J.; Létourneau, R.; Okusaka, T.; Funakoshi, A.; Furuse, J.; Park, Y.S.; Ohkawa, S. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: A double-blind randomised phase 3 study. Lancet Oncol., 2011, 12(3), 256-262.
[http://dx.doi.org/10.1016/S1470-2045(11)70004-3] [PMID: 21306953]
[48]
Awasthi, N.; Schwarz, M.A.; Schwarz, R.E. Antitumour activity of sunitinib in combination with gemcitabine in experimental pancreatic cancer. HPB, 2011, 13(9), 597-604.
[http://dx.doi.org/10.1111/j.1477-2574.2011.00333.x] [PMID: 21843259]
[49]
Bergmann, L.; Maute, L.; Heil, G.; Rüssel, J.; Weidmann, E.; Köberle, D.; Fuxius, S.; Weigang-Köhler, K.; Aulitzky, W.; Wörmann, B. A prospective randomised phase-II trial with gemcitabine versus gemcitabine plus sunitinib in advanced pancreatic cancer: A study of the CESAR central european society for anticancer drug research–EWIV. Eur. J. Cancer, 2015, 51(1), 27-36.
[http://dx.doi.org/10.1016/j.ejca.2014.10.010] [PMID: 25459392]
[50]
Pant, S.; Martin, L.K.; Geyer, S.; Wei, L.; Van Loon, K.; Sommovilla, N.; Zalupski, M.; Iyer, R.; Fogelman, D.; Ko, A.H. Treatment-related hypertension as a pharmacodynamic biomarker for the efficacy of bevacizumab in advanced pancreas cancer: A pooled analysis of 4 prospective trials of gemcitabine-based therapy with bevacizumab. Am. J. Clin. Oncol., 2016, 39(6), 614-618.
[http://dx.doi.org/10.1097/COC.0000000000000108] [PMID: 25068471]
[51]
Awasthi, N.; Hinz, S.; Brekken, R.A.; Schwarz, M.A.; Schwarz, R.E. Nintedanib, a triple angiokinase inhibitor, enhances cytotoxic therapy response in pancreatic cancer. Cancer Lett., 2015, 358(1), 59-66.
[http://dx.doi.org/10.1016/j.canlet.2014.12.027] [PMID: 25527450]
[52]
Bill, R.; Fagiani, E.; Zumsteg, A.; Antoniadis, H.; Johansson, D.; Haefliger, S.; Albrecht, I.; Hilberg, F.; Christofori, G. Nintedanib is a highly effective therapeutic for neuroendocrine carcinoma of the pancreas (PNET) in the Rip1Tag2 transgenic mouse model. Clin. Cancer Res., 2015, 21(21), 4856-4867.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-3036] [PMID: 26206868]
[53]
Faloppi, L.; Bianconi, M.; Giampieri, R.; Sobrero, A.; Labianca, R.; Ferrari, D.; Barni, S.; Aitini, E.; Zaniboni, A.; Boni, C. The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib. Oncotarget, 2015, 6(33), 35087-35094.
[http://dx.doi.org/10.18632/oncotarget.5197] [PMID: 26397228]
[54]
Wegner, C.S.; Hauge, A.; Simonsen, T.G.; Gaustad, J-V.; Andersen, L.M.K.; Rofstad, E.K. DCE-MRI of sunitinib-induced changes in tumor microvasculature and hypoxia: A study of pancreatic ductal adenocarcinoma xenografts. Neoplasia, 2018, 20(7), 734-744.
[http://dx.doi.org/10.1016/j.neo.2018.05.006] [PMID: 29886124]
[55]
O’Reilly, E.M.; Niedzwiecki, D.; Hall, M.; Hollis, D.; Bekaii-Saab, T.; Pluard, T.; Douglas, K.; Abou-Alfa, G.K.; Kindler, H.L.; Schilsky, R.L. A cancer and leukemia group B phase II study of sunitinib malate in patients with previously treated metastatic pancreatic adenocarcinoma (CALGB 80603). Oncol, 2010, 15(12), 1310-1319.
[http://dx.doi.org/10.1634/theoncologist.2010-0152] [PMID: 21148613]
[56]
Grande, E.; Rodriguez-Antona, C.; López, C.; Alonso-Gordoa, T.; Benavent, M.; Capdevila, J.; Teulé, A.; Custodio, A.; Sevilla, I.; Hernando, J. Sunitinib and evofosfamide (TH-302) in systemic treatment-naive patients with grade 1/2 metastatic pancreatic neuroendocrine tumors: The GETNE-1408 trial. Oncol, 2021, 26(11), 941-949.
[http://dx.doi.org/10.1002/onco.13885] [PMID: 34190375]
[57]
Bendell, J.C.; Zakari, A.; Lang, E.; Waterhouse, D.; Flora, D.; Alguire, K.; McCleod, M.; Peacock, N.; Ruehlman, P.; Lane, C.M. A phase II study of the combination of bevacizumab, pertuzumab, and octreotide LAR for patients with advanced neuroendocrine cancers. Cancer Invest., 2016, 34(5), 213-219.
[http://dx.doi.org/10.3109/07357907.2016.1174257] [PMID: 27127841]
[58]
Reni, M.; Cereda, S.; Milella, M.; Novarino, A.; Passardi, A.; Mambrini, A.; Di Lucca, G.; Aprile, G.; Belli, C.; Danova, M. Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: A phase II randomised trial. Eur. J. Cancer, 2013, 49(17), 3609-3615.
[http://dx.doi.org/10.1016/j.ejca.2013.06.041] [PMID: 23899530]
[59]
Jain, R.K. Antiangiogenesis strategies revisited: From starving tumors to alleviating hypoxia. Cancer Cell, 2014, 26(5), 605-622.
[http://dx.doi.org/10.1016/j.ccell.2014.10.006] [PMID: 25517747]
[60]
Zhou, P.; Li, B.; Liu, F.; Zhang, M.; Wang, Q.; Liu, Y.; Yao, Y.; Li, D. The epithelial to mesenchymal transition (EMT) and cancer stem cells: Implication for treatment resistance in pancreatic cancer. Mol. Cancer, 2017, 16, 1-52.
[http://dx.doi.org/10.1186/s12943-017-0624-9] [PMID: 28245823]
[61]
Ribatti, D. Tumor refractoriness to anti-VEGF therapy. Oncotarget, 2016, 7(29), 46668-46677.
[http://dx.doi.org/10.18632/oncotarget.8694] [PMID: 27081695]
[62]
Zang, J.; Liang, X.; Huang, Y.; Jia, Y.; Li, X.; Xu, W.; Chou, C.J.; Zhang, Y. Discovery of novel pazopanib-based HDAC and VEGFR dual inhibitors targeting cancer epigenetics and angiogenesis simultaneously. J. Med. Chem., 2018, 61(12), 5304-5322.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00384] [PMID: 29787262]
[63]
Aggarwal, R.; Thomas, S.; Pawlowska, N.; Bartelink, I.; Grabowsky, J.; Jahan, T.; Cripps, A.; Harb, A.; Leng, J.; Reinert, A. Inhibiting histone deacetylase as a means to reverse resistance to angiogenesis inhibitors: Phase I study of abexinostat plus pazopanib in advanced solid tumor malignancies. J. Clin. Oncol., 2017, 35(11), 1231-1239.
[http://dx.doi.org/10.1200/JCO.2016.70.5350] [PMID: 28221861]
[64]
Barnes, J.A.; Redd, R.; Fisher, D.C.; Hochberg, E.P.; Takvorian, T.; Neuberg, D.; Jacobsen, E.; Abramson, J.S. Panobinostat in combination with rituximab in heavily pretreated diffuse large B-cell lymphoma: Results of a phase II study. Hematol. Oncol., 2018, 36(4), 633-637.
[http://dx.doi.org/10.1002/hon.2515] [PMID: 29956350]
[65]
Di Federico, A.; Mosca, M.; Pagani, R.; Carloni, R.; Frega, G.; De Giglio, A.; Rizzo, A.; Ricci, D.; Tavolari, S.; Di Marco, M. Immunotherapy in pancreatic cancer: Why do we keep failing? A focus on tumor immune microenvironment, predictive biomarkers and treatment outcomes. Cancers, 2022, 14(10), 2429.
[http://dx.doi.org/10.3390/cancers14102429] [PMID: 35626033]
[66]
McCormick, K.A.; Coveler, A.L.; Rossi, G.R.; Vahanian, N.N.; Link, C.; Chiorean, E.G. Pancreatic cancer: Update on immunotherapies and algenpantucel-L. Hum. Vaccin. Immunother., 2016, 12(3), 563-575.
[http://dx.doi.org/10.1080/21645515.2015.1093264] [PMID: 26619245]
[67]
Luo, W.; Yang, G.; Luo, W.; Cao, Z.; Liu, Y.; Qiu, J.; Chen, G.; You, L.; Zhao, F.; Zheng, L. Novel therapeutic strategies and perspectives for metastatic pancreatic cancer: Vaccine therapy is more than just a theory. Cancer Cell Int., 2020, 20(1), 66.
[http://dx.doi.org/10.1186/s12935-020-1147-9] [PMID: 32158356]
[68]
Miyazawa, M.; Katsuda, M.; Maguchi, H.; Katanuma, A.; Ishii, H.; Ozaka, M.; Yamao, K.; Imaoka, H.; Kawai, M.; Hirono, S. Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients. Int. J. Cancer, 2017, 140(4), 973-982.
[http://dx.doi.org/10.1002/ijc.30510] [PMID: 27861852]
[69]
Mucileanu, A.; Chira, R.; Mircea, P.A. PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies. Med. Pharm. Rep., 2021, 94(4), 402-410.
[http://dx.doi.org/10.15386/mpr-2116] [PMID: 36105495]
[70]
Bengsch, F.; Knoblock, D.M.; Liu, A.; McAllister, F.; Beatty, G.L. CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer. Cancer Immunol. Immunother., 2017, 66(12), 1609-1617.
[http://dx.doi.org/10.1007/s00262-017-2053-4] [PMID: 28856392]
[71]
Seifert, L.; Plesca, I.; Müller, L.; Sommer, U.; Heiduk, M.; von Renesse, J.; Digomann, D.; Glück, J.; Klimova, A.; Weitz, J. LAG-3-expressing tumor-infiltrating T cells are associated with reduced disease-free survival in pancreatic cancer. Cancers, 2021, 13(6), 1297.
[http://dx.doi.org/10.3390/cancers13061297] [PMID: 33803936]
[72]
Peng, P-j.; Li, Y.; Sun, S. On the significance of Tim-3 expression in pancreatic cancer. Saudi J. Biol. Sci., 2017, 24(8), 1754-1757.
[http://dx.doi.org/10.1016/j.sjbs.2017.11.006] [PMID: 29551917]
[73]
Noubissi Nzeteu, G.A.; Gibbs, B.F.; Kotnik, N.; Troja, A.; Bockhorn, M.; Meyer, N.H. Nanoparticle-based immunotherapy of pancreatic cancer. Front. Mol. Biosci., 2022, 9, 948898.
[http://dx.doi.org/10.3389/fmolb.2022.948898] [PMID: 36106025]
[74]
Hou, Z.; Pan, Y.; Fei, Q.; Lin, Y.; Zhou, Y.; Liu, Y.; Guan, H.; Yu, X.; Lin, X.; Lu, F. Prognostic significance and therapeutic potential of the immune checkpoint VISTA in pancreatic cancer. J. Cancer Res. Clin. Oncol., 2021, 147, 517-531.
[http://dx.doi.org/10.1007/s00432-020-03463-9] [PMID: 33237432]
[75]
Muth, S.T.; Saung, M.T.; Blair, A.B.; Henderson, M.G.; Thomas, D.L., II; Zheng, L. CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma. Cancer Lett., 2021, 499, 99-108.
[http://dx.doi.org/10.1016/j.canlet.2020.11.041] [PMID: 33271264]
[76]
Starzer, A.M.; Berghoff, A.S. New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). ESMO Open, 2019, 4, e000629.
[http://dx.doi.org/10.1136/esmoopen-2019-000629] [PMID: 32152062]
[77]
Yeo, D.; Giardina, C.; Saxena, P.; Rasko, J.E. The next wave of cellular immunotherapies in pancreatic cancer. Mol. Ther. Oncolytics, 2022, 24, 561-576.
[http://dx.doi.org/10.1016/j.omto.2022.01.010] [PMID: 35229033]
[78]
Lim, C.Y.; Chang, J.H.; Lee, W.S.; Kim, J.; Park, I.Y. CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 and suppress human pancreatic cancer in organotypic slice cultures. Gut Liver, 2022, 16(4), 645-659.
[http://dx.doi.org/10.5009/gnl210311] [PMID: 34933280]
[79]
Vence, L.; Bucktrout, S.L.; Fernandez Curbelo, I.; Blando, J.; Smith, B.M.; Mahne, A.E.; Lin, J.C.; Park, T.; Pascua, E.; Sai, T. Characterization and comparison of GITR expression in solid tumors. Clin. Cancer Res., 2019, 25(21), 6501-6510.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-0289] [PMID: 31358539]
[80]
Yadav, R.; Redmond, W.L. Current clinical trial landscape of OX40 agonists. Curr. Oncol. Rep., 2022, 24(7), 951-960.
[http://dx.doi.org/10.1007/s11912-022-01265-5] [PMID: 35352295]
[81]
Kadomoto, S.; Izumi, K.; Mizokami, A. Roles of CCL2-CCR2 axis in the tumor microenvironment. Int. J. Mol. Sci., 2021, 22(16), 8530.
[http://dx.doi.org/10.3390/ijms22168530] [PMID: 34445235]
[82]
Xu, M.; Wang, Y.; Xia, R.; Wei, Y.; Wei, X. Role of the CCL2-CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting. Cell Prolif., 2021, 54(10), e13115.
[http://dx.doi.org/10.1111/cpr.13115] [PMID: 34464477]
[83]
Meireson, A.; Devos, M.; Brochez, L. Ido expression in cancer: Different compartment, different functionality? Front. Immunol., 2020, 11, 531491.
[http://dx.doi.org/10.3389/fimmu.2020.531491] [PMID: 33072086]
[84]
Shen, W.; Tao, G-Q.; Zhang, Y.; Cai, B.; Sun, J.; Tian, Z-Q. Tgf-β in pancreatic cancer initiation and progression: Two sides of the same coin. Cell Biosci., 2017, 7, 1-39.
[http://dx.doi.org/10.1186/s13578-017-0168-0] [PMID: 28794854]
[85]
Padoan, A.; Plebani, M.; Basso, D. Inflammation and pancreatic cancer: Focus on metabolism, cytokines, and immunity. Int. J. Mol. Sci., 2019, 20(3), 676.
[http://dx.doi.org/10.3390/ijms20030676] [PMID: 30764482]
[86]
Candido, J.B.; Morton, J.P.; Bailey, P.; Campbell, A.D.; Karim, S.A.; Jamieson, T.; Lapienyte, L.; Gopinathan, A.; Clark, W.; McGhee, E.J. CSF1R+ macrophages sustain pancreatic tumor growth through T cell suppression and maintenance of key gene programs that define the squamous subtype. Cell Rep., 2018, 23(5), 1448-1460.
[http://dx.doi.org/10.1016/j.celrep.2018.03.131] [PMID: 29719257]
[87]
Xia, C.; Yin, S.; To, K.K.; Fu, L. CD39/CD73/A2AR pathway and cancer immunotherapy. Mol. Cancer, 2023, 22(1), 1-17.
[http://dx.doi.org/10.1186/s12943-023-01733-x] [PMID: 36859386]
[88]
Matkar, P.N.; Jong, E.D.; Ariyagunarajah, R.; Prud’homme, G.J.; Singh, K.K.; Leong-Poi, H. Jack of many trades: Multifaceted role of neuropilins in pancreatic cancer. Cancer Med., 2018, 7(10), 5036-5046.
[http://dx.doi.org/10.1002/cam4.1715] [PMID: 30216699]
[89]
Henriksen, A.; Dyhl-Polk, A.; Chen, I.; Nielsen, D. Checkpoint inhibitors in pancreatic cancer. Cancer Treat. Rev., 2019, 78, 17-30.
[http://dx.doi.org/10.1016/j.ctrv.2019.06.005] [PMID: 31325788]
[90]
Li, H-B.; Yang, Z-H.; Guo, Q-Q. Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: Limitations and prospects: A systematic review. Cell Commun. Signal., 2021, 19, 117.
[http://dx.doi.org/10.1186/s12964-021-00789-w] [PMID: 34819086]
[91]
Darvin, P.; Toor, S.M.; Sasidharan Nair, V.; Elkord, E. Immune checkpoint inhibitors: Recent progress and potential biomarkers. Exp. Mol. Med., 2018, 50(12), 1-11.
[http://dx.doi.org/10.1038/s12276-018-0191-1] [PMID: 30546008]
[92]
Johansson, H.; Andersson, R.; Bauden, M.; Hammes, S.; Holdenrieder, S.; Ansari, D. Immune checkpoint therapy for pancreatic cancer. World J. Gastroenterol., 2016, 22(43), 9457-9476.
[http://dx.doi.org/10.3748/wjg.v22.i43.9457] [PMID: 27920468]
[93]
Macherla, S.; Laks, S.; Naqash, A.R.; Bulumulle, A.; Zervos, E.; Muzaffar, M. Emerging role of immune checkpoint blockade in pancreatic cancer. Int. J. Mol. Sci., 2018, 19(11), 3505.
[http://dx.doi.org/10.3390/ijms19113505] [PMID: 30405053]
[94]
Bian, J.; Almhanna, K. Pancreatic cancer and immune checkpoint inhibitors—still a long way to go. Transl. Gastroenterol. Hepatol., 2021, 6.
[http://dx.doi.org/10.21037/tgh.2020.04.03] [PMID: 33409400]
[95]
Patel, K.; Siraj, S.; Smith, C.; Nair, M.; Vishwanatha, J.K.; Basha, R. Pancreatic cancer: An emphasis on current perspectives in immunotherapy. Crit. Rev. Oncog., 2019, 24(2), 105-118.
[http://dx.doi.org/10.1615/CritRevOncog.2019031417] [PMID: 31679206]
[96]
Hargadon, K.M.; Johnson, C.E.; Williams, C.J. Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Int. Immunopharmacol., 2018, 62, 29-39.
[http://dx.doi.org/10.1016/j.intimp.2018.06.001] [PMID: 29990692]
[97]
Varghese, A.M. Chimeric antigen receptor (CAR) T and other T cell strategies for pancreas adenocarcinoma. Linchuang Zhongliuxue Zazhi, 2017, 6(6), 66-66.
[http://dx.doi.org/10.21037/cco.2017.09.04] [PMID: 29156888]
[98]
Yoon, J.H.; Jung, Y-J.; Moon, S-H. Immunotherapy for pancreatic cancer. World J. Clin. Cases, 2021, 9(13), 2969-2982.
[http://dx.doi.org/10.12998/wjcc.v9.i13.2969] [PMID: 33969083]
[99]
de Miguel, M.; Calvo, E. Clinical challenges of immune checkpoint inhibitors. Cancer Cell, 2020, 38(3), 326-333.
[http://dx.doi.org/10.1016/j.ccell.2020.07.004] [PMID: 32750319]
[100]
Shi, Y.; Li, Y.; Wu, B.; Zhong, C.; Lang, Q.; Liang, Z.; Zhang, Y.; Lv, C.; Han, S.; Yu, Y. Normalization of tumor vasculature: A potential strategy to increase the efficiency of immune checkpoint blockades in cancers. Int. Immunopharmacol., 2022, 110, 108968.
[http://dx.doi.org/10.1016/j.intimp.2022.108968] [PMID: 35764018]

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