Pharmacological Inhibition of Exosome Machinery: An Emerging
Prospect in Cancer Therapeutics

Saima      Syeda; Kavita      Rawat; Anju      Shrivastava
doi:10.2174/1568009622666220401093316
Abstract

Exosomes are nanocarriers that mediate intercellular communication crucial for normal physiological functions. However, exponentially emerging reports have correlated their dysregulated release with various pathologies, including cancer. In cancer, from stromal remodeling to metastasis, where tumor cells bypass the immune surveillance and show drug resistivity, it has been established to be mediated via tumor-derived exosomes. Owing to their role in cancer pathogenicity, exosomebased strategies offer enormous potential in treatment regimens. These strategies include the use of exosomes as a drug carrier or as an immunotherapeutic agent, which requires advanced nanotechnologies for exosome isolation and characterization. In contrast, pharmacological inhibition of exosome machinery surpasses the requisites of nanotechnology and thus emerges as an essential prospect in cancer therapeutics. In this line, researchers are currently trying to dissect the molecular pathways to reveal the involvement of key regulatory proteins that facilitate the release of tumor-derived exosomes. Subsequently, screening of various molecules in targeting these proteins, with eventual abatement of exosome-induced cancer pathogenicity, is being done. However, their clinical translation requires more extensive studies. Here, we comprehensively review the molecular mechanisms regulating exosome release in cancer. Moreover, we provide insight into the key findings that highlight the effect of various drugs as exosome blockers, which will add to the route of drug development in cancer management.
Keywords: Tumor-derived exosomes, regulatory proteins, exosome blockers, cancer therapeutics, nanocarriers, drug resistivity.
« Previous Next »
Graphical Abstract

[1] 
Soung, Y.H.; Nguyen, T.; Cao, H.; Lee, J.; Chung, J. Emerging roles of exosomes in cancer invasion and metastasis. BMB Rep.,  2016, 49(1), 18-25.
[http://dx.doi.org/10.5483/BMBRep.2016.49.1.239] [PMID: 26592936] 
[2] 
Willms, E.; Johansson, H.J.; Mäger, I.; Lee, Y.; Blomberg, K.E.M.; Sadik, M.; Alaarg, A.; Smith, C.I.; Lehtiö, J.; El Andaloussi, S.; Wood, M.J.; Vader, P. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci. Rep.,  2016, 6(1), 22519.
[http://dx.doi.org/10.1038/srep22519] [PMID: 26931825] 
[3] 
Caby, M-P.; Lankar, D.; Vincendeau-Scherrer, C.; Raposo, G.; Bonnerot, C. Exosomal-like vesicles are present in human blood plasma. Int. Immunol.,  2005, 17(7), 879-887.
[http://dx.doi.org/10.1093/intimm/dxh267] [PMID: 15908444] 
[4] 
Pisitkun, T.; Shen, R-F.; Knepper, M.A. Identification and proteomic profiling of exosomes in human urine. Proc. Natl. Acad. Sci. USA,  2004, 101(36), 13368-13373.
[http://dx.doi.org/10.1073/pnas.0403453101] [PMID: 15326289] 
[5] 
Street, J.M.; Barran, P.E.; Mackay, C.L.; Weidt, S.; Balmforth, C.; Walsh, T.S.; Chalmers, R.T.; Webb, D.J.; Dear, J.W. Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J. Transl. Med.,  2012, 10(1), 5.
[http://dx.doi.org/10.1186/1479-5876-10-5] [PMID: 22221959] 
[6] 
Admyre, C.; Johansson, S.M.; Qazi, K.R.; Filén, J-J.; Lahesmaa, R.; Norman, M.; Neve, E.P.; Scheynius, A.; Gabrielsson, S. Exosomes with immune modulatory features are present in human breast milk. J. Immunol.,  2007, 179(3), 1969-1978.
[http://dx.doi.org/10.4049/jimmunol.179.3.1969] [PMID: 17641064] 
[7] 
Ogawa, Y.; Kanai-Azuma, M.; Akimoto, Y.; Kawakami, H.; Yanoshita, R. Exosome-like vesicles with dipeptidyl peptidase IV in human saliva. Biol. Pharm. Bull.,  2008, 31(6), 1059-1062.
[http://dx.doi.org/10.1248/bpb.31.1059] [PMID: 18520029] 
[8] 
Atay, S.; Godwin, A.K. Tumor-derived exosomes: A message delivery system for tumor progression. Commun. Integr. Biol.,  2014, 7(1), e28231.
[http://dx.doi.org/10.4161/cib.28231] [PMID: 24778765] 
[9] 
Vella, L.; Sharples, R.; Lawson, V.; Masters, C.; Cappai, R.; Hill, A. Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J. Pathol.,  2007, 211(5), 582-590.
[10] 
Li, X.; Corbett, A.L.; Taatizadeh, E.; Tasnim, N.; Little, J.P.; Garnis, C.; Daugaard, M.; Guns, E.; Hoorfar, M.; Li, I.T.S. Challenges and opportunities in exosome research-Perspectives from biology, engineering, and cancer therapy. APL Bioeng.,  2019, 3(1), 011503.
[http://dx.doi.org/10.1063/1.5087122] [PMID: 31069333] 
[11] 
Giusti, I.; Delle Monache, S.; Di Francesco, M.; Sanità, P.; D’Ascenzo, S.; Gravina, G.L.; Festuccia, C.; Dolo, V. From glioblastoma to endothelial cells through extracellular vesicles: Messages for angiogenesis. Tumour Biol.,  2016, 37(9), 12743-12753.
[http://dx.doi.org/10.1007/s13277-016-5165-0] [PMID: 27448307] 
[12] 
Safaei, R.; Larson, B.J.; Cheng, T.C.; Gibson, M.A.; Otani, S.; Naerdemann, W.; Howell, S.B. Abnormal lysosomal trafficking and en-hanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol. Cancer Ther.,  2005, 4(10), 1595-1604.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0102] [PMID: 16227410] 
[13] 
Torreggiani, E.; Roncuzzi, L.; Perut, F.; Zini, N.; Baldini, N. Multimodal transfer of MDR by exosomes in human osteosarcoma. Int. J. Oncol.,  2016, 49(1), 189-196.
[http://dx.doi.org/10.3892/ijo.2016.3509] [PMID: 27176642] 
[14] 
Ning, K.; Wang, T.; Sun, X.; Zhang, P.; Chen, Y.; Jin, J.; Hua, D. UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer. J. Surg. Oncol.,  2017, 115(8), 932-940.
[http://dx.doi.org/10.1002/jso.24614] [PMID: 28334432] 
[15] 
Yang, S.J.; Wang, D.D.; Li, J.; Xu, H.Z.; Shen, H.Y.; Chen, X.; Zhou, S.Y.; Zhong, S.L.; Zhao, J.H.; Tang, J.H. Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast cancer. Gene,  2017, 623, 5-14.
[http://dx.doi.org/10.1016/j.gene.2017.04.031] [PMID: 28438694] 
[16] 
Mears, R.; Craven, R.A.; Hanrahan, S.; Totty, N.; Upton, C.; Young, S.L.; Patel, P.; Selby, P.J.; Banks, R.E. Proteomic analysis of melano-ma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics,  2004, 4(12), 4019-4031.
[http://dx.doi.org/10.1002/pmic.200400876] [PMID: 15478216] 
[17] 
Staubach, S.; Razawi, H.; Hanisch, F.G. Proteomics of MUC1-containing lipid rafts from plasma membranes and exosomes of human breast carcinoma cells MCF-7. Proteomics,  2009, 9(10), 2820-2835.
[http://dx.doi.org/10.1002/pmic.200800793] [PMID: 19415654] 
[18] 
Navabi, H.; Croston, D.; Hobot, J.; Clayton, A.; Zitvogel, L.; Jasani, B.; Bailey-Wood, R.; Wilson, K.; Tabi, Z.; Mason, M.D.; Adams, M. Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial. Blood Cells Mol. Dis.,  2005, 35(2), 149-152.
[http://dx.doi.org/10.1016/j.bcmd.2005.06.008] [PMID: 16061407] 
[19] 
Nilsson, J.; Skog, J.; Nordstrand, A.; Baranov, V.; Mincheva-Nilsson, L.; Breakefield, X.O.; Widmark, A. Prostate cancer-derived urine exosomes: A novel approach to biomarkers for prostate cancer. Br. J. Cancer,  2009, 100(10), 1603-1607.
[http://dx.doi.org/10.1038/sj.bjc.6605058] [PMID: 19401683] 
[20] 
Xue, H.; Lü, B.; Zhang, J.; Wu, M.; Huang, Q.; Wu, Q.; Sheng, H.; Wu, D.; Hu, J.; Lai, M. Identification of serum biomarkers for colorectal cancer metastasis using a differential secretome approach. J. Proteome Res.,  2010, 9(1), 545-555.
[http://dx.doi.org/10.1021/pr9008817] [PMID: 19924834] 
[21] 
Graner, M.W.; Alzate, O.; Dechkovskaia, A.M.; Keene, J.D.; Sampson, J.H.; Mitchell, D.A.; Bigner, D.D. Proteomic and immunologic analyses of brain tumor exosomes. FASEB J.,  2009, 23(5), 1541-1557.
[http://dx.doi.org/10.1096/fj.08-122184] [PMID: 19109410] 
[22] 
Al-Nedawi, K.; Meehan, B.; Micallef, J.; Lhotak, V.; May, L.; Guha, A.; Rak, J. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol.,  2008, 10(5), 619-624.
[http://dx.doi.org/10.1038/ncb1725] [PMID: 18425114] 
[23] 
Demory Beckler, M.; Higginbotham, J.N.; Franklin, J.L.; Ham, A-J.; Halvey, P.J.; Imasuen, I.E.; Whitwell, C.; Li, M.; Liebler, D.C.; Coffey, R.J. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol. Cell. Proteomics,  2013, 12(2), 343-355.
[http://dx.doi.org/10.1074/mcp.M112.022806] [PMID: 23161513] 
[24] 
Hao, S.; Ye, Z.; Li, F.; Meng, Q.; Qureshi, M.; Yang, J.; Xiang, J. Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. Exp. Oncol.,  2006, 28(2), 126-131.
[PMID: 16837903] 
[25] 
Baroni, S.; Romero-Cordoba, S.; Plantamura, I.; Dugo, M.; D’ippolito, E.; Cataldo, A.; Cosentino, G.; Angeloni, V.; Rossini, A.; Daidone, M. Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts. Cell Death Dis.,  2016, 7(7), e2312-e.
[http://dx.doi.org/10.1038/cddis.2016.224] 
[26] 
Zhou, X.; Yan, T.; Huang, C.; Xu, Z.; Wang, L.; Jiang, E.; Wang, H.; Chen, Y.; Liu, K.; Shao, Z.; Shang, Z. Melanoma cell-secreted exo-somal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway. J. Exp. Clin. Cancer Res.,  2018, 37(1), 242.
[http://dx.doi.org/10.1186/s13046-018-0911-3] [PMID: 30285793] 
[27] 
Ding, L.; Ren, J.; Zhang, D.; Li, Y.; Huang, X.; Hu, Q.; Wang, H.; Song, Y.; Ni, Y.; Hou, Y. A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of oral squamous cell carcinoma via LncRNA-CAF/interleukin-33. Carcinogenesis,  2018, 39(3), 397-406.
[http://dx.doi.org/10.1093/carcin/bgy006] [PMID: 29346528] 
[28] 
Ringuette Goulet, C.; Bernard, G.; Tremblay, S.; Chabaud, S.; Bolduc, S.; Pouliot, F. Exosomes induce fibroblast differentiation into can-cer-associated fibroblasts through TGFβ signaling. Mol. Cancer Res.,  2018, 16(7), 1196-1204.
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0784] [PMID: 29636362] 
[29] 
Ekström, E.J.; Bergenfelz, C.; von Bülow, V.; Serifler, F.; Carlemalm, E.; Jönsson, G.; Andersson, T.; Leandersson, K. WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells. Mol. Cancer,  2014, 13(1), 88.
[http://dx.doi.org/10.1186/1476-4598-13-88] [PMID: 24766647] 
[30] 
Wang, J.; De Veirman, K.; Faict, S.; Frassanito, M.A.; Ribatti, D.; Vacca, A.; Menu, E. Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression. J. Pathol.,  2016, 239(2), 162-173.
[http://dx.doi.org/10.1002/path.4712] [PMID: 26956697] 
[31] 
Chan, Y.K.; Zhang, H.; Liu, P.; Tsao, S.W.; Lung, M.L.; Mak, N.K.; Ngok-Shun Wong, R.; Ying-Kit Yue, P. Proteomic analysis of exo-somes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins. Int. J. Cancer,  2015, 137(8), 1830-1841.
[http://dx.doi.org/10.1002/ijc.29562] [PMID: 25857718] 
[32] 
You, B.; Cao, X.; Shao, X.; Ni, H.; Shi, S.; Shan, Y.; Gu, Z.; You, Y. Clinical and biological significance of HAX-1 overexpression in na-sopharyngeal carcinoma. Oncotarget,  2016, 7(11), 12505-12524.
[http://dx.doi.org/10.18632/oncotarget.7274] [PMID: 26871467] 
[33] 
Wilson, C.M.; Naves, T.; Vincent, F.; Melloni, B.; Bonnaud, F.; Lalloué, F.; Jauberteau, M-O. Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors. J. Cell Sci.,  2014, 127(Pt 18), 3983-3997.
[http://dx.doi.org/10.1242/jcs.149336] [PMID: 25037567] 
[34] 
Maji, S.; Chaudhary, P.; Akopova, I.; Nguyen, P.M.; Hare, R.J.; Gryczynski, I.; Vishwanatha, J.K. Exosomal annexin II promotes angio-genesis and breast cancer metastasis. Mol. Cancer Res.,  2017, 15(1), 93-105.
[http://dx.doi.org/10.1158/1541-7786.MCR-16-0163] [PMID: 27760843] 
[35] 
Zhou, W.; Fong, M.Y.; Min, Y.; Somlo, G.; Liu, L.; Palomares, M.R.; Yu, Y.; Chow, A.; O’Connor, S.T.F.; Chin, A.R.; Yen, Y.; Wang, Y.; Marcusson, E.G.; Chu, P.; Wu, J.; Wu, X.; Li, A.X.; Li, Z.; Gao, H.; Ren, X.; Boldin, M.P.; Lin, P.C.; Wang, S.E. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell,  2014, 25(4), 501-515.
[http://dx.doi.org/10.1016/j.ccr.2014.03.007] [PMID: 24735924] 
[36] 
Beckham, C.J.; Olsen, J.; Yin, P-N.; Wu, C-H.; Ting, H-J.; Hagen, F.K.; Scosyrev, E.; Messing, E.M.; Lee, Y-F. Bladder cancer exo-somes contain EDIL-3/Del1 and facilitate cancer progression. J. Urol.,  2014, 192(2), 583-592.
[http://dx.doi.org/10.1016/j.juro.2014.02.035] [PMID: 24530986] 
[37] 
Fang, J.H.; Zhang, Z.J.; Shang, L.R.; Luo, Y.W.; Lin, Y.F.; Yuan, Y.; Zhuang, S.M. Hepatoma cell-secreted exosomal microRNA-103 in-creases vascular permeability and promotes metastasis by targeting junction proteins. Hepatology,  2018, 68(4), 1459-1475.
[http://dx.doi.org/10.1002/hep.29920] [PMID: 29637568] 
[38] 
Gabrusiewicz, K.; Li, X.; Wei, J.; Hashimoto, Y.; Marisetty, A.L.; Ott, M.; Wang, F.; Hawke, D.; Yu, J.; Healy, L.M.; Hossain, A.; Akers, J.C.; Maiti, S.N.; Yamashita, S.; Shimizu, Y.; Dunner, K.; Zal, M.A.; Burks, J.K.; Gumin, J.; Nwajei, F.; Rezavanian, A.; Zhou, S.; Rao, G.; Sawaya, R.; Fuller, G.N.; Huse, J.T.; Antel, J.P.; Li, S.; Cooper, L.; Sulman, E.P.; Chen, C.; Geula, C.; Kalluri, R.; Zal, T.; Heimberger, A.B. Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes. OncoImmunology,  2018, 7(4), e1412909.
[http://dx.doi.org/10.1080/2162402X.2017.1412909] [PMID: 29632728] 
[39] 
Cooks, T.; Pateras, I.S.; Jenkins, L.M.; Patel, K.M.; Robles, A.I.; Morris, J.; Forshew, T.; Appella, E.; Gorgoulis, V.G.; Harris, C.C. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat. Commun.,  2018, 9(1), 771.
[http://dx.doi.org/10.1038/s41467-018-03224-w] [PMID: 29472616] 
[40] 
Yin, C.; Han, Q.; Xu, D.; Zheng, B.; Zhao, X.; Zhang, J. SALL4-mediated upregulation of exosomal miR-146a-5p drives T-cell exhaustion by M2 tumor-associated macrophages in HCC. OncoImmunology,  2019, 8(7), 1601479.
[http://dx.doi.org/10.1080/2162402X.2019.1601479] [PMID: 31143524] 
[41] 
Szczepanski, M.J.; Szajnik, M.; Welsh, A.; Whiteside, T.L.; Boyiadzis, M. Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-β1. Haematologica,  2011, 96(9), 1302-1309.
[http://dx.doi.org/10.3324/haematol.2010.039743] [PMID: 21606166] 
[42] 
Zhang, X.; Shi, H.; Yuan, X.; Jiang, P.; Qian, H.; Xu, W. Tumor-derived exosomes induce N2 polarization of neutrophils to promote gas-tric cancer cell migration. Mol. Cancer,  2018, 17(1), 1-16.
[http://dx.doi.org/10.1186/s12943-017-0753-1] [PMID: 29304823] 
[43] 
Hwang, W-L.; Lan, H-Y.; Cheng, W-C.; Huang, S-C.; Yang, M-H. Tumor stem-like cell-derived exosomal RNAs prime neutrophils for facilitating tumorigenesis of colon cancer. J. Hematol. Oncol.,  2019, 12(1), 10.
[http://dx.doi.org/10.1186/s13045-019-0699-4] [PMID: 30683126] 
[44] 
Clayton, A.; Mitchell, J.P.; Court, J.; Linnane, S.; Mason, M.D.; Tabi, Z. Human tumor-derived exosomes down-modulate NKG2D ex-pression. J. Immunol.,  2008, 180(11), 7249-7258.
[45] 
Abusamra, A.J.; Zhong, Z.; Zheng, X.; Li, M.; Ichim, T.E.; Chin, J.L.; Min, W-P. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol. Dis.,  2005, 35(2), 169-173.
[http://dx.doi.org/10.1016/j.bcmd.2005.07.001] [PMID: 16081306] 
[46] 
Szajnik, M.; Czystowska, M.; Szczepanski, M.J.; Mandapathil, M.; Whiteside, T.L. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One,  2010, 5(7), e11469.
[http://dx.doi.org/10.1371/journal.pone.0011469] [PMID: 20661468] 
[47] 
Chalmin, F.; Ladoire, S.; Mignot, G.; Vincent, J.; Bruchard, M.; Remy-Martin, J-P.; Boireau, W.; Rouleau, A.; Simon, B.; Lanneau, D.; De Thonel, A.; Multhoff, G.; Hamman, A.; Martin, F.; Chauffert, B.; Solary, E.; Zitvogel, L.; Garrido, C.; Ryffel, B.; Borg, C.; Apetoh, L.; Ré-bé, C.; Ghiringhelli, F. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J. Clin. Invest.,  2010, 120(2), 457-471.
[http://dx.doi.org/10.1172/JCI40483] [PMID: 20093776] 
[48] 
Rahman, M.A.; Barger, J.F.; Lovat, F.; Gao, M.; Otterson, G.A.; Nana-Sinkam, P. Lung cancer exosomes as drivers of epithelial mesen-chymal transition. Oncotarget,  2016, 7(34), 54852-54866.
[http://dx.doi.org/10.18632/oncotarget.10243] [PMID: 27363026] 
[49] 
You, Y.; Shan, Y.; Chen, J.; Yue, H.; You, B.; Shi, S.; Li, X.; Cao, X. Matrix metalloproteinase 13-containing exosomes promote nasopha-ryngeal carcinoma metastasis. Cancer Sci.,  2015, 106(12), 1669-1677.
[http://dx.doi.org/10.1111/cas.12818] [PMID: 26362844] 
[50] 
Ramteke, A.; Ting, H.; Agarwal, C.; Mateen, S.; Somasagara, R.; Hussain, A.; Graner, M.; Frederick, B.; Agarwal, R.; Deep, G. Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Mol. Carcinog.,  2015, 54(7), 554-565.
[http://dx.doi.org/10.1002/mc.22124] [PMID: 24347249] 
[51] 
Sánchez, C.A.; Andahur, E.I.; Valenzuela, R.; Castellón, E.A.; Fullá, J.A.; Ramos, C.G.; Triviño, J.C. Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche. Oncotarget,  2016, 7(4), 3993-4008.
[http://dx.doi.org/10.18632/oncotarget.6540] [PMID: 26675257] 
[52] 
Wang, X.; Luo, G.; Zhang, K.; Cao, J.; Huang, C.; Jiang, T.; Liu, B.; Su, L.; Qiu, Z. Correction: Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Cancer Res.,  2020, 80(4), 922.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-3872] [PMID: 32060228] 
[53] 
Tauro, B.J.; Mathias, R.A.; Greening, D.W.; Gopal, S.K.; Ji, H.; Kapp, E.A.; Coleman, B.M.; Hill, A.F.; Kusebauch, U.; Hallows, J.L.; Sht-eynberg, D.; Moritz, R.L.; Zhu, H.J.; Simpson, R.J. Oncogenic H-ras reprograms Madin-Darby canine kidney (MDCK) cell-derived exo-somal proteins following epithelial-mesenchymal transition. Mol. Cell. Proteomics,  2013, 12(8), 2148-2159.
[http://dx.doi.org/10.1074/mcp.M112.027086] [PMID: 23645497] 
[54] 
McCready, J.; Sims, J.D.; Chan, D.; Jay, D.G. Secretion of extracellular hsp90α via exosomes increases cancer cell motility: A role for plasminogen activation. BMC Cancer,  2010, 10(1), 294.
[http://dx.doi.org/10.1186/1471-2407-10-294] [PMID: 20553606] 
[55] 
Ciravolo, V.; Huber, V.; Ghedini, G.C.; Venturelli, E.; Bianchi, F.; Campiglio, M.; Morelli, D.; Villa, A.; Della Mina, P.; Menard, S.; Fil-ipazzi, P.; Rivoltini, L.; Tagliabue, E.; Pupa, S.M. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based ther-apy. J. Cell. Physiol.,  2012, 227(2), 658-667.
[http://dx.doi.org/10.1002/jcp.22773] [PMID: 21465472] 
[56] 
Paggetti, J.; Haderk, F.; Seiffert, M.; Janji, B.; Distler, U.; Ammerlaan, W.; Kim, Y.J.; Adam, J.; Lichter, P.; Solary, E.; Berchem, G.; Mous-say, E. Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts. Blood,  2015, 126(9), 1106-1117.
[http://dx.doi.org/10.1182/blood-2014-12-618025] [PMID: 26100252] 
[57] 
van den Boorn, J.G.; Dassler, J.; Coch, C.; Schlee, M.; Hartmann, G. Exosomes as nucleic acid nanocarriers. Adv. Drug Deliv. Rev.,  2013, 65(3), 331-335.
[http://dx.doi.org/10.1016/j.addr.2012.06.011] [PMID: 22750807] 
[58] 
Hanson, P.I.; Cashikar, A. Multivesicular body morphogenesis. Annu. Rev. Cell Dev. Biol.,  2012, 28, 337-362.
[http://dx.doi.org/10.1146/annurev-cellbio-092910-154152] [PMID: 22831642] 
[59] 
Sexton, R.E.; Mpilla, G.; Kim, S.; Philip, P.A.; Azmi, A.S. Ras and exosome signaling. Semin. Cancer Biol.,  2019, 54, 131-137.
[60] 
Zheng, Z-Y.; Xu, L.; Bar-Sagi, D.; Chang, E.C. Escorting Ras. Small GTPases,  2012, 3(4), 236-239.
[http://dx.doi.org/10.4161/sgtp.20460] [PMID: 22735486] 
[61] 
Imjeti, N.S.; Menck, K.; Egea-Jimenez, A.L.; Lecointre, C.; Lembo, F.; Bouguenina, H.; Badache, A.; Ghossoub, R.; David, G.; Roche, S.; Zimmermann, P. Syntenin mediates SRC function in exosomal cell-to-cell communication. Proc. Natl. Acad. Sci. USA,  2017, 114(47), 12495-12500.
[http://dx.doi.org/10.1073/pnas.1713433114] [PMID: 29109268] 
[62] 
Hikita, T.; Kuwahara, A.; Watanabe, R.; Miyata, M.; Oneyama, C. Src in endosomal membranes promotes exosome secretion and tumor progression. Sci. Rep.,  2019, 9(1), 3265.
[http://dx.doi.org/10.1038/s41598-019-39882-z] [PMID: 30824759] 
[63] 
Fares, J.; Kashyap, R.; Zimmermann, P. Syntenin: Key player in cancer exosome biogenesis and uptake? Cell Adhes. Migr.,  2017, 11(2), 124-126.
[http://dx.doi.org/10.1080/19336918.2016.1225632] [PMID: 27589080] 
[64] 
Baietti, M.F.; Zhang, Z.; Mortier, E.; Melchior, A.; Degeest, G.; Geeraerts, A.; Ivarsson, Y.; Depoortere, F.; Coomans, C.; Vermeiren, E.; Zimmermann, P.; David, G. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol.,  2012, 14(7), 677-685.
[http://dx.doi.org/10.1038/ncb2502] [PMID: 22660413] 
[65] 
Ilan, N.; Elkin, M.; Vlodavsky, I. Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Int. J. Biochem. Cell Biol.,  2006, 38(12), 2018-2039.
[http://dx.doi.org/10.1016/j.biocel.2006.06.004] [PMID: 16901744] 
[66] 
Ramani, V.C.; Purushothaman, A.; Stewart, M.D.; Thompson, C.A.; Vlodavsky, I.; Au, J.L.S.; Sanderson, R.D. The heparanase/syndecan-1 axis in cancer: Mechanisms and therapies. FEBS J.,  2013, 280(10), 2294-2306.
[http://dx.doi.org/10.1111/febs.12168] [PMID: 23374281] 
[67] 
Roucourt, B.; Meeussen, S.; Bao, J.; Zimmermann, P.; David, G. Heparanase activates the syndecan-syntenin-ALIX exosome pathway. Cell Res.,  2015, 25(4), 412-428.
[http://dx.doi.org/10.1038/cr.2015.29] [PMID: 25732677] 
[68] 
Thompson, C.A.; Purushothaman, A.; Ramani, V.C.; Vlodavsky, I.; Sanderson, R.D. Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes. J. Biol. Chem.,  2013, 288(14), 10093-10099.
[http://dx.doi.org/10.1074/jbc.C112.444562] [PMID: 23430739] 
[69] 
Bandari, S.K.; Purushothaman, A.; Ramani, V.C.; Brinkley, G.J.; Chandrashekar, D.S.; Varambally, S.; Mobley, J.A.; Zhang, Y.; Brown, E.E.; Vlodavsky, I.; Sanderson, R.D. Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior. Matrix Biol.,  2018, 65, 104-118.
[http://dx.doi.org/10.1016/j.matbio.2017.09.001] [PMID: 28888912] 
[70] 
Stuffers, S.; Sem Wegner, C.; Stenmark, H.; Brech, A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic,  2009, 10(7), 925-937.
[http://dx.doi.org/10.1111/j.1600-0854.2009.00920.x] [PMID: 19490536] 
[71] 
Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Takeshita, F.; Matsuki, Y.; Ochiya, T. Secretory mechanisms and intercellular transfer of mi-croRNAs in living cells. J. Biol. Chem.,  2010, 285(23), 17442-17452.
[http://dx.doi.org/10.1074/jbc.M110.107821] [PMID: 20353945] 
[72] 
Kosaka, N.; Iguchi, H.; Hagiwara, K.; Yoshioka, Y.; Takeshita, F.; Ochiya, T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J. Biol. Chem.,  2013, 288(15), 10849-10859.
[http://dx.doi.org/10.1074/jbc.M112.446831] [PMID: 23439645] 
[73] 
Trajkovic, K.; Hsu, C.; Chiantia, S.; Rajendran, L.; Wenzel, D.; Wieland, F.; Schwille, P.; Brügger, B.; Simons, M. Ceramide triggers bud-ding of exosome vesicles into multivesicular endosomes. Science,  2008, 319(5867), 1244-1247.
[http://dx.doi.org/10.1126/science.1153124] [PMID: 18309083] 
[74] 
Croce, C.M. Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet.,  2009, 10(10), 704-714.
[http://dx.doi.org/10.1038/nrg2634] [PMID: 19763153] 
[75] 
Lawrie, C.H.; Gal, S.; Dunlop, H.M.; Pushkaran, B.; Liggins, A.P.; Pulford, K.; Banham, A.H.; Pezzella, F.; Boultwood, J.; Wainscoat, J.S.; Hatton, C.S.; Harris, A.L. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lym-phoma. Br. J. Haematol.,  2008, 141(5), 672-675.
[http://dx.doi.org/10.1111/j.1365-2141.2008.07077.x] [PMID: 18318758] 
[76] 
Mitchell, P.S.; Parkin, R.K.; Kroh, E.M.; Fritz, B.R.; Wyman, S.K.; Pogosova-Agadjanyan, E.L.; Peterson, A.; Noteboom, J.; O’Briant, K.C.; Allen, A.; Lin, D.W.; Urban, N.; Drescher, C.W.; Knudsen, B.S.; Stirewalt, D.L.; Gentleman, R.; Vessella, R.L.; Nelson, P.S.; Martin, D.B.; Tewari, M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA,  2008, 105(30), 10513-10518.
[http://dx.doi.org/10.1073/pnas.0804549105] [PMID: 18663219] 
[77] 
Chen, X.; Ba, Y.; Ma, L.; Cai, X.; Yin, Y.; Wang, K.; Guo, J.; Zhang, Y.; Chen, J.; Guo, X.; Li, Q.; Li, X.; Wang, W.; Zhang, Y.; Wang, J.; Jiang, X.; Xiang, Y.; Xu, C.; Zheng, P.; Zhang, J.; Li, R.; Zhang, H.; Shang, X.; Gong, T.; Ning, G.; Wang, J.; Zen, K.; Zhang, J.; Zhang, C.Y. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res.,  2008, 18(10), 997-1006.
[http://dx.doi.org/10.1038/cr.2008.282] [PMID: 18766170] 
[78] 
Taylor, D.D.; Gercel-Taylor, C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol. Oncol.,  2008, 110(1), 13-21.
[http://dx.doi.org/10.1016/j.ygyno.2008.04.033] [PMID: 18589210] 
[79] 
Cheng, Q.; Li, X.; Wang, Y.; Dong, M.; Zhan, F.H.; Liu, J. The ceramide pathway is involved in the survival, apoptosis and exosome func-tions of human multiple myeloma cells in vitro. Acta Pharmacol. Sin.,  2018, 39(4), 561-568.
[http://dx.doi.org/10.1038/aps.2017.118] [PMID: 28858294] 
[80] 
Koppers-Lalic, D.; Hackenberg, M.; Bijnsdorp, I.V.; van Eijndhoven, M.A.J.; Sadek, P.; Sie, D.; Zini, N.; Middeldorp, J.M.; Ylstra, B.; de Menezes, R.X.; Würdinger, T.; Meijer, G.A.; Pegtel, D.M. Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep.,  2014, 8(6), 1649-1658.
[http://dx.doi.org/10.1016/j.celrep.2014.08.027] [PMID: 25242326] 
[81] 
Wu, B.; Su, S.; Patil, D.P.; Liu, H.; Gan, J.; Jaffrey, S.R.; Ma, J. Molecular basis for the specific and multivariant recognitions of RNA sub-strates by human hnRNP A2/B1. Nat. Commun.,  2018, 9(1), 420.
[http://dx.doi.org/10.1038/s41467-017-02770-z] [PMID: 29379020] 
[82] 
Cha, D.J.; Franklin, J.L.; Dou, Y.; Liu, Q.; Higginbotham, J.N.; Demory Beckler, M.; Weaver, A.M.; Vickers, K.; Prasad, N.; Levy, S.; Zhang, B.; Coffey, R.J.; Patton, J.G. KRAS-dependent sorting of miRNA to exosomes. eLife,  2015, 4, e07197.
[http://dx.doi.org/10.7554/eLife.07197] [PMID: 26132860] 
[83] 
McKenzie, A.J.; Hoshino, D.; Hong, N.H.; Cha, D.J.; Franklin, J.L.; Coffey, R.J.; Patton, J.G.; Weaver, A.M. KRAS-MEK signaling controls Ago2 sorting into exosomes. Cell Rep.,  2016, 15(5), 978-987.
[http://dx.doi.org/10.1016/j.celrep.2016.03.085] [PMID: 27117408] 
[84] 
Kowal, J.; Tkach, M.; Théry, C. Biogenesis and secretion of exosomes. Curr. Opin. Cell Biol.,  2014, 29, 116-125.
[http://dx.doi.org/10.1016/j.ceb.2014.05.004] [PMID: 24959705] 
[85] 
Ostrowski, M.; Carmo, N.B.; Krumeich, S.; Fanget, I.; Raposo, G.; Savina, A.; Moita, C.F.; Schauer, K.; Hume, A.N.; Freitas, R.P.; Goud, B.; Benaroch, P.; Hacohen, N.; Fukuda, M.; Desnos, C.; Seabra, M.C.; Darchen, F.; Amigorena, S.; Moita, L.F.; Thery, C. Rab27a and Rab27b control different steps of the exosome secretion
pathway. Nat. Cell Biol.,  2010, 12(1), 19-30-1-13.
[86] 
Blanc, L.; Vidal, M. New insights into the function of Rab GTPases in the context of exosomal secretion. Small GTPases,  2018, 9(1-2), 95-106.
[http://dx.doi.org/10.1080/21541248.2016.1264352] [PMID: 28135905] 
[87] 
Tzeng, H-T.; Wang, Y-C. Rab-mediated vesicle trafficking in cancer. J. Biomed. Sci.,  2016, 23(1), 70.
[http://dx.doi.org/10.1186/s12929-016-0287-7] [PMID: 27716280] 
[88] 
Bobrie, A.; Krumeich, S.; Reyal, F.; Recchi, C.; Moita, L.F.; Seabra, M.C.; Ostrowski, M.; Théry, C. Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res.,  2012, 72(19), 4920-4930.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-0925] [PMID: 22865453] 
[89] 
Ostenfeld, M.S.; Jeppesen, D.K.; Laurberg, J.R.; Boysen, A.T.; Bramsen, J.B.; Primdal-Bengtson, B.; Hendrix, A.; Lamy, P.; Dagnaes-Hansen, F.; Rasmussen, M.H.; Bui, K.H.; Fristrup, N.; Christensen, E.I.; Nordentoft, I.; Morth, J.P.; Jensen, J.B.; Pedersen, J.S.; Beck, M.; Theodorescu, D.; Borre, M.; Howard, K.A.; Dyrskjøt, L.; Ørntoft, T.F. Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer Res.,  2014, 74(20), 5758-5771.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-3512] [PMID: 25261234] 
[90] 
Peinado, H. Alečković M.; Lavotshkin, S.; Matei, I.; Costa-Silva, B.; Moreno-Bueno, G.; Hergueta-Redondo, M.; Williams, C.; García-Santos, G.; Ghajar, C.; Nitadori-Hoshino, A.; Hoffman, C.; Badal, K.; Garcia, B.A.; Callahan, M.K.; Yuan, J.; Martins, V.R.; Skog, J.; Kaplan, R.N.; Brady, M.S.; Wolchok, J.D.; Chapman, P.B.; Kang, Y.; Bromberg, J.; Lyden, D. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med.,  2012, 18(6), 883-891.
[http://dx.doi.org/10.1038/nm.2753] [PMID: 22635005] 
[91] 
Desdín-Micó, G.; Mittelbrunn, M. Role of exosomes in the protection of cellular homeostasis. Cell Adhes. Migr.,  2017, 11(2), 127-134.
[http://dx.doi.org/10.1080/19336918.2016.1251000] [PMID: 27875097] 
[92] 
Parolini, I.; Federici, C.; Raggi, C.; Lugini, L.; Palleschi, S.; De Milito, A.; Coscia, C.; Iessi, E.; Logozzi, M.; Molinari, A.; Colone, M.; Tatti, M.; Sargiacomo, M.; Fais, S. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J. Biol. Chem.,  2009, 284(49), 34211-34222.
[http://dx.doi.org/10.1074/jbc.M109.041152] [PMID: 19801663] 
[93] 
Savina, A.; Furlán, M.; Vidal, M.; Colombo, M.I. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J. Biol. Chem.,  2003, 278(22), 20083-20090.
[http://dx.doi.org/10.1074/jbc.M301642200] [PMID: 12639953] 
[94] 
Taylor, J.M.; Simpson, R.U. Inhibition of cancer cell growth by calcium channel antagonists in the athymic mouse. Cancer Res.,  1992, 52(9), 2413-2418.
[PMID: 1533173] 
[95] 
Messenger, S.W.; Woo, S.S.; Sun, Z.; Martin, T.F.J. Correction: A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4. J. Cell Biol.,  2019, 218(4), 1423.
[http://dx.doi.org/10.1083/jcb.20171013203042019c] [PMID: 30852488] 
[96] 
Savina, A.; Fader, C.M.; Damiani, M.T.; Colombo, M.I. Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner. Traffic,  2005, 6(2), 131-143.
[http://dx.doi.org/10.1111/j.1600-0854.2004.00257.x] [PMID: 15634213] 
[97] 
Kholia, S.; Jorfi, S.; Thompson, P.R.; Causey, C.P.; Nicholas, A.P.; Inal, J.M.; Lange, S. A novel role for peptidylarginine deiminases in microvesicle release reveals therapeutic potential of PAD inhibition in sensitizing prostate cancer cells to chemotherapy. J. Extracell. Vesicles,  2015, 4(1), 26192.
[http://dx.doi.org/10.3402/jev.v4.26192] [PMID: 26095379] 
[98] 
Kosgodage, U.S.; Uysal-Onganer, P.; MacLatchy, A.; Kraev, I.; Chatterton, N.P.; Nicholas, A.P.; Inal, J.M.; Lange, S. Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and MicroRNAs in glioblastoma multi-forme. Int. J. Mol. Sci.,  2018, 20(1), 103.
[http://dx.doi.org/10.3390/ijms20010103] [PMID: 30597867] 
[99] 
Logozzi, M.; Spugnini, E.; Mizzoni, D.; Di Raimo, R.; Fais, S. Extracellular acidity and increased exosome release as key phenotypes of malignant tumors. Cancer Metastasis Rev.,  2019, 38(1-2), 93-101.
[http://dx.doi.org/10.1007/s10555-019-09783-8] [PMID: 30715644] 
[100] 
Huang, Z.; Yang, M.; Li, Y.; Yang, F.; Feng, Y. Exosomes derived from hypoxic colorectal cancer cells transfer Wnt4 to normoxic cells to elicit a prometastatic phenotype. Int. J. Biol. Sci.,  2018, 14(14), 2094-2102.
[http://dx.doi.org/10.7150/ijbs.28288] [PMID: 30585272] 
[101] 
Panigrahi, G.K.; Praharaj, P.P.; Peak, T.C.; Long, J.; Singh, R.; Rhim, J.S.; Abd Elmageed, Z.Y.; Deep, G. Hypoxia-induced exosome secre-tion promotes survival of African-American and Caucasian prostate cancer cells. Sci. Rep.,  2018, 8(1), 1-13.
[PMID: 29311619] 
[102] 
Logozzi, M.; Capasso, C.; Di Raimo, R.; Del Prete, S.; Mizzoni, D.; Falchi, M.; Supuran, C.T.; Fais, S. Prostate cancer cells and exosomes in acidic condition show increased carbonic anhydrase IX expression and activity. J. Enzyme Inhib. Med. Chem.,  2019, 34(1), 272-278.
[http://dx.doi.org/10.1080/14756366.2018.1538980] [PMID: 30734594] 
[103] 
Logozzi, M.; Mizzoni, D.; Angelini, D.F.; Di Raimo, R.; Falchi, M.; Battistini, L.; Fais, S. Microenvironmental pH and exosome levels interplay in human cancer cell lines of different histotypes. Cancers (Basel),  2018, 10(10), 370.
[http://dx.doi.org/10.3390/cancers10100370] [PMID: 30301144] 
[104] 
Boussadia, Z.; Lamberti, J.; Mattei, F.; Pizzi, E.; Puglisi, R.; Zanetti, C.; Pasquini, L.; Fratini, F.; Fantozzi, L.; Felicetti, F.; Fecchi, K.; Raggi, C.; Sanchez, M.; D’Atri, S.; Carè, A.; Sargiacomo, M.; Parolini, I. Acidic microenvironment plays a key role in human melanoma progres-sion through a sustained exosome mediated transfer of clinically relevant metastatic molecules. J. Exp. Clin. Cancer Res.,  2018, 37(1), 245.
[http://dx.doi.org/10.1186/s13046-018-0915-z] [PMID: 30290833] 
[105] 
Federici, C.; Petrucci, F.; Caimi, S.; Cesolini, A.; Logozzi, M.; Borghi, M.; D’Ilio, S.; Lugini, L.; Violante, N.; Azzarito, T.; Majorani, C.; Brambilla, D.; Fais, S. Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. PLoS One,  2014, 9(2), e88193.
[http://dx.doi.org/10.1371/journal.pone.0088193] [PMID: 24516610] 
[106] 
Logozzi, M.; Mizzoni, D.; Capasso, C.; Del Prete, S.; Di Raimo, R.; Falchi, M.; Angelini, D.F.; Sciarra, A.; Maggi, M.; Supuran, C.T.; Fais, S. Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH. J. Enzyme Inhib. Med. Chem.,  2020, 35(1), 280-288.
[http://dx.doi.org/10.1080/14756366.2019.1697249] [PMID: 31790614] 
[107] 
Wu, H.; Zhao, H.; Chen, L. Deoxyshikonin inhibits viability and glycolysis by suppressing the Akt/mTOR pathway in acute myeloid leu-kemia cells. Front. Oncol.,  2020, 10, 1253.
[http://dx.doi.org/10.3389/fonc.2020.01253] [PMID: 32850379] 
[108] 
Wei, Y.; Wang, D.; Jin, F.; Bian, Z.; Li, L.; Liang, H.; Li, M.; Shi, L.; Pan, C.; Zhu, D.; Chen, X.; Hu, G.; Liu, Y.; Zhang, C.Y.; Zen, K. Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23. Nat. Commun.,  2017, 8(1), 14041.
[http://dx.doi.org/10.1038/ncomms14041] [PMID: 28067230] 
[109] 
Wang, Y.; Zhang, Y.; Cai, G.; Li, Q. Exosomes as actively targeted nanocarriers for cancer therapy. Int. J. Nanomedicine,  2020, 15, 4257-4273.
[http://dx.doi.org/10.2147/IJN.S239548] [PMID: 32606676] 
[110] 
Rashed, M.H.; Bayraktar, E.; Helal, G.K.; Abd-Ellah, M.F.; Amero, P.; Chavez-Reyes, A.; Rodriguez-Aguayo, C. Exosomes: From garbage bins to promising therapeutic targets. Int. J. Mol. Sci.,  2017, 18(3), 538.
[http://dx.doi.org/10.3390/ijms18030538] 
[111] 
Nam, G.H.; Choi, Y.; Kim, G.B.; Kim, S.; Kim, S.A.; Kim, I.S. Emerging prospects of exosomes for cancer treatment: From conventional therapy to immunotherapy. Adv. Mater.,  2020, 32(51), e2002440.
[http://dx.doi.org/10.1002/adma.202002440] [PMID: 33015883] 
[112] 
Cho, K-N.; Lee, K-I. Chemistry and biology of Ras farnesyltransferase. Arch. Pharm. Res.,  2002, 25(6), 759-769.
[http://dx.doi.org/10.1007/BF02976989] [PMID: 12510823] 
[113] 
Datta, A.; Kim, H.; Lal, M.; McGee, L.; Johnson, A.; Moustafa, A.A.; Jones, J.C.; Mondal, D.; Ferrer, M.; Abdel-Mageed, A.B. Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells. Cancer Lett.,  2017, 408, 73-81.
[http://dx.doi.org/10.1016/j.canlet.2017.08.020] [PMID: 28844715] 
[114] 
Datta, A.; Kim, H.; McGee, L.; Johnson, A.E.; Talwar, S.; Marugan, J.; Southall, N.; Hu, X.; Lal, M.; Mondal, D.; Ferrer, M.; Abdel-Mageed, A.B. High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer. Sci. Rep.,  2018, 8(1), 8161.
[http://dx.doi.org/10.1038/s41598-018-26411-7] [PMID: 29802284] 
[115] 
Thomas, X.; Elhamri, M. Tipifarnib in the treatment of acute myeloid leukemia. Biologics,  2007, 1(4), 415-424.
[PMID: 19707311] 
[116] 
Karp, J.E.; Lancet, J.E. Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics,  2008, 2(3), 491-500.
[PMID: 19707379] 
[117] 
Martin, L-A.; Head, J.E.; Pancholi, S.; Salter, J.; Quinn, E.; Detre, S.; Kaye, S.; Howes, A.; Dowsett, M.; Johnston, S.R. The farnesyltrans-ferase inhibitor R115777 (tipifarnib) in combination with tamoxifen acts synergistically to inhibit MCF-7 breast cancer cell proliferation and cell cycle progression in vitro and in vivo. Mol. Cancer Ther.,  2007, 6(9), 2458-2467.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0452] [PMID: 17876043] 
[118] 
Delmas, C.; End, D.; Rochaix, P.; Favre, G.; Toulas, C.; Cohen-Jonathan, E. The farnesyltransferase inhibitor R115777 reduces hypoxia and matrix metalloproteinase 2 expression in human glioma xenograft. Clin. Cancer Res.,  2003, 9(16 Pt 1), 6062-6068.
[PMID: 14676133] 
[119] 
Asai, H.; Ikezu, S.; Tsunoda, S.; Medalla, M.; Luebke, J.; Haydar, T.; Wolozin, B.; Butovsky, O.; Kügler, S.; Ikezu, T. Depletion of micro-glia and inhibition of exosome synthesis halt tau propagation. Nat. Neurosci.,  2015, 18(11), 1584-1593.
[http://dx.doi.org/10.1038/nn.4132] [PMID: 26436904] 
[120] 
Dinkins, M.B.; Dasgupta, S.; Wang, G.; Zhu, G.; Bieberich, E. Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol. Aging,  2014, 35(8), 1792-1800.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.02.012] [PMID: 24650793] 
[121] 
Matsumoto, A.; Takahashi, Y.; Nishikawa, M.; Sano, K.; Morishita, M.; Charoenviriyakul, C.; Saji, H.; Takakura, Y. Accelerated growth of B16BL6 tumor in mice through efficient uptake of their own exosomes by B16BL6 cells. Cancer Sci.,  2017, 108(9), 1803-1810.
[http://dx.doi.org/10.1111/cas.13310] [PMID: 28667694] 
[122] 
Nakamura, K.; Sawada, K.; Kinose, Y.; Yoshimura, A.; Toda, A.; Nakatsuka, E.; Hashimoto, K.; Mabuchi, S.; Morishige, K.I.; Kurachi, H.; Lengyel, E.; Kimura, T. Exosomes promote ovarian cancer cell invasion through transfer of CD44 to peritoneal mesothelial cells. Mol. Cancer Res.,  2017, 15(1), 78-92.
[http://dx.doi.org/10.1158/1541-7786.MCR-16-0191] [PMID: 27758876] 
[123] 
Fabbri, M.; Paone, A.; Calore, F.; Galli, R.; Gaudio, E.; Santhanam, R.; Lovat, F.; Fadda, P.; Mao, C.; Nuovo, G.J.; Zanesi, N.; Crawford, M.; Ozer, G.H.; Wernicke, D.; Alder, H.; Caligiuri, M.A.; Nana-Sinkam, P.; Perrotti, D.; Croce, C.M. MicroRNAs bind to Toll-like recep-tors to induce prometastatic inflammatory response. Proc. Natl. Acad. Sci. USA,  2012, 109(31), E2110-E2116.
[http://dx.doi.org/10.1073/pnas.1209414109] [PMID: 22753494] 
[124] 
Yang, Y.; Li, C-W.; Chan, L-C.; Wei, Y.; Hsu, J-M.; Xia, W.; Cha, J-H.; Hou, J.; Hsu, J.L.; Sun, L.; Hung, M.C. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res.,  2018, 28(8), 862-864.
[http://dx.doi.org/10.1038/s41422-018-0060-4] [PMID: 29959401] 
[125] 
Faict, S.; Muller, J.; De Veirman, K.; De Bruyne, E.; Maes, K.; Vrancken, L.; Heusschen, R.; De Raeve, H.; Schots, R.; Vanderkerken, K.; Caers, J.; Menu, E. Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteo-blasts. Blood Cancer J.,  2018, 8(11), 105.
[http://dx.doi.org/10.1038/s41408-018-0139-7] [PMID: 30409995] 
[126] 
Li, X-Q.; Liu, J-T.; Fan, L-L.; Liu, Y.; Cheng, L.; Wang, F.; Yu, H-Q.; Gao, J.; Wei, W.; Wang, H.; Sun, G.P. Exosomes derived from ge-fitinib-treated EGFR-mutant lung cancer cells alter cisplatin sensitivity via up-regulating autophagy. Oncotarget,  2016, 7(17), 24585-24595.
[http://dx.doi.org/10.18632/oncotarget.8358] [PMID: 27029054] 
[127] 
Cao, Y.L.; Zhuang, T.; Xing, B.H.; Li, N.; Li, Q. Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer. Cell Biochem. Funct.,  2017, 35(6), 296-303.
[http://dx.doi.org/10.1002/cbf.3276] [PMID: 28791708] 
[128] 
Sweeney, R.; Richards, K.E.; Hill, R. Gemcitabine-induced exosome
hypersecretion increases the chemoresistance and migration
of pancreatic cancer cells. FASEB J.,  2017, 31(1_supplement), 775.20.
[129] 
Kosgodage, U.S.; Trindade, R.P.; Thompson, P.R.; Inal, J.M.; Lange, S. Chloramidine/bisindolylmaleimide-I-mediated inhibition of exo-some and microvesicle release and enhanced efficacy of cancer chemotherapy. Int. J. Mol. Sci.,  2017, 18(5), 1007.
[http://dx.doi.org/10.3390/ijms18051007] [PMID: 28486412] 
[130] 
Kosgodage, U.S.; Mould, R.; Henley, A.B.; Nunn, A.V.; Guy, G.W.; Thomas, E.L.; Inal, J.M.; Bell, J.D.; Lange, S. Cannabidiol (CBD) is a novel inhibitor for exosome and microvesicle (EMV) release in cancer. Front. Pharmacol.,  2018, 9, 889.
[http://dx.doi.org/10.3389/fphar.2018.00889] [PMID: 30150937] 
[131] 
Escrevente, C.; Keller, S.; Altevogt, P.; Costa, J. Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer,  2011, 11(1), 108.
[http://dx.doi.org/10.1186/1471-2407-11-108] [PMID: 21439085] 
[132] 
Khan, S.; Jutzy, J.M.; Aspe, J.R.; McGregor, D.W.; Neidigh, J.W.; Wall, N.R. Survivin is released from cancer cells via exosomes. Apoptosis,  2011, 16(1), 1-12.
[http://dx.doi.org/10.1007/s10495-010-0534-4] [PMID: 20717727] 
[133] 
Ding, Y.; Zhang, H.; Zhou, Z.; Zhong, M.; Chen, Q.; Wang, X.; Zhu, Z. u-PA inhibitor amiloride suppresses peritoneal metastasis in gas-tric cancer. World J. Surg. Oncol.,  2012, 10(1), 270.
[http://dx.doi.org/10.1186/1477-7819-10-270] [PMID: 23234499] 
[134] 
Zheng, Y.T.; Yang, H.Y.; Li, T.; Zhao, B.; Shao, T.F.; Xiang, X.Q.; Cai, W.M. Amiloride sensitizes human pancreatic cancer cells to erlo-tinib in vitro through inhibition of the PI3K/AKT signaling pathway. Acta Pharmacol. Sin.,  2015, 36(5), 614-626.
[http://dx.doi.org/10.1038/aps.2015.4] [PMID: 25864651] 
[135] 
Rojas, E.A.; Corchete, L.A.; San-Segundo, L.; Martínez-Blanch, J.F.; Codoñer, F.M.; Paíno, T.; Puig, N.; García-Sanz, R.; Mateos, M.V.; Ocio, E.M.; Misiewicz-Krzeminska, I.; Gutiérrez, N.C. Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myelo-ma. Clin. Cancer Res.,  2017, 23(21), 6602-6615.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0678] [PMID: 28790111] 
[136] 
Kim, H.J.; Park, M.K.; Kim, S.Y.; Lee, C.H. Novel suppressive effects of ketotifen on migration and invasion of MDA-MB-231 and HT-1080 cancer cells. Biomol. Ther. (Seoul),  2014, 22(6), 540-546.
[http://dx.doi.org/10.4062/biomolther.2014.081] [PMID: 25489422] 
[137] 
Faustino-Rocha, A.I.; Gama, A.; Neuparth, M.J.; Oliveira, P.A.; Ferreira, R.; Ginja, M. Mast cells in mammary carcinogenesis: Host or tumor supporters? Anticancer Res.,  2017, 37(3), 1013-1021.
[http://dx.doi.org/10.21873/anticanres.11411] [PMID: 28314259] 
[138] 
Khan, F.M.; Saleh, E.; Alawadhi, H.; Harati, R.; Zimmermann, W-H.; El-Awady, R. Inhibition of exosome release by ketotifen enhances sensitivity of cancer cells to doxorubicin. Cancer Biol. Ther.,  2018, 19(1), 25-33.
[http://dx.doi.org/10.1080/15384047.2017.1394544] [PMID: 29244610] 
[139] 
Pisanti, S.; Malfitano, A.M.; Ciaglia, E.; Lamberti, A.; Ranieri, R.; Cuomo, G.; Abate, M.; Faggiana, G.; Proto, M.C.; Fiore, D.; Laezza, C.; Bifulco, M. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol. Ther.,  2017, 175, 133-150.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.041] [PMID: 28232276] 
[140] 
Velasco, G.; Hernández-Tiedra, S.; Dávila, D.; Lorente, M. The use of cannabinoids as anticancer agents. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2016, 64, 259-266.
[http://dx.doi.org/10.1016/j.pnpbp.2015.05.010] [PMID: 26071989] 
[141] 
Kosgodage, U.S.; Uysal-Onganer, P.; MacLatchy, A.; Mould, R.; Nunn, A.V.; Guy, G.W.; Kraev, I.; Chatterton, N.P.; Thomas, E.L.; Inal, J.M.; Bell, J.D.; Lange, S. Cannabidiol affects extracellular vesicle release, miR21 and miR126, and reduces prohibitin protein in glioblas-toma multiforme cells. Transl. Oncol.,  2019, 12(3), 513-522.
[http://dx.doi.org/10.1016/j.tranon.2018.12.004] [PMID: 30597288] 
[142] 
Wei, Y.; Li, M.; Cui, S.; Wang, D.; Zhang, C-Y.; Zen, K.; Li, L. Shikonin inhibits the proliferation of human breast cancer cells by reduc-ing tumor-derived exosomes. Molecules,  2016, 21(6), 777.
[http://dx.doi.org/10.3390/molecules21060777] [PMID: 27322220] 
[143] 
Chen, J.; Xie, J.; Jiang, Z.; Wang, B.; Wang, Y.; Hu, X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene,  2011, 30(42), 4297-4306.
[http://dx.doi.org/10.1038/onc.2011.137] [PMID: 21516121] 
[144] 
Zhao, X.; Zhu, Y.; Hu, J.; Jiang, L.; Li, L.; Jia, S.; Zen, K. Shikonin inhibits tumor growth in mice by suppressing pyruvate kinase M2-mediated aerobic glycolysis. Sci. Rep.,  2018, 8(1), 14517.
[http://dx.doi.org/10.1038/s41598-018-31615-y] [PMID: 30266938] 
[145] 
Kastelein, F.; Spaander, M.C.; Steyerberg, E.W.; Biermann, K.; Valkhoff, V.E.; Kuipers, E.J.; Bruno, M.J.; Group, P.S. Proton pump inhib-itors reduce the risk of neoplastic progression in patients with Barrett’s esophagus. Clin. Gastroenterol. Hepatol.,  2013, 11(4), 382-388.
[http://dx.doi.org/10.1016/j.cgh.2012.11.014] [PMID: 23200977] 
[146] 
Spugnini, E.P.; Baldi, A.; Buglioni, S.; Carocci, F.; de Bazzichini, G.M.; Betti, G.; Pantaleo, I.; Menicagli, F.; Citro, G.; Fais, S. Lansopra-zole as a rescue agent in chemoresistant tumors: A phase I/II study in companion animals with spontaneously occurring tumors. J. Transl. Med.,  2011, 9(1), 221.
[http://dx.doi.org/10.1186/1479-5876-9-221] [PMID: 22204495] 
[147] 
Spugnini, E.P.; Buglioni, S.; Carocci, F.; Francesco, M.; Vincenzi, B.; Fanciulli, M.; Fais, S. High dose lansoprazole combined with metro-nomic chemotherapy: A phase I/II study in companion animals with spontaneously occurring tumors. J. Transl. Med.,  2014, 12(1), 225.
[http://dx.doi.org/10.1186/s12967-014-0225-y] [PMID: 25143012] 
[148] 
Canitano, A.; Iessi, E.; Spugnini, E.P.; Federici, C.; Fais, S. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma. Cancer Lett.,  2016, 376(2), 278-283.
[http://dx.doi.org/10.1016/j.canlet.2016.04.015] [PMID: 27084522] 
[149] 
Lugini, L.; Federici, C.; Borghi, M.; Azzarito, T.; Marino, M.L.; Cesolini, A.; Spugnini, E.P.; Fais, S. Proton pump inhibitors while belong-ing to the same family of generic drugs show different anti-tumor effect. J. Enzyme Inhib. Med. Chem.,  2016, 31(4), 538-545.
[http://dx.doi.org/10.3109/14756366.2015.1046062] [PMID: 26018420] 
[150] 
Guan, X-W.; Zhao, F.; Wang, J-Y.; Wang, H-Y.; Ge, S-H.; Wang, X.; Zhang, L.; Liu, R.; Ba, Y.; Li, H-L.; Deng, T.; Zhou, L.K.; Bai, M.; Ning, T.; Zhang, H.Y.; Huang, D.Z. Tumor microenvironment interruption: A novel anti-cancer mechanism of Proton-pump inhibitor in gastric cancer by suppressing the release of microRNA-carrying exosomes. Am. J. Cancer Res.,  2017, 7(9), 1913-1925.
[PMID: 28979813] 
[151] 
Luciani, F.; Spada, M.; De Milito, A.; Molinari, A.; Rivoltini, L.; Montinaro, A.; Marra, M.; Lugini, L.; Logozzi, M.; Lozupone, F.; Federi-ci, C.; Iessi, E.; Parmiani, G.; Arancia, G.; Belardelli, F.; Fais, S. Effect of proton pump inhibitor pretreatment on resistance of solid tu-mors to cytotoxic drugs. J. Natl. Cancer Inst.,  2004, 96(22), 1702-1713.
[http://dx.doi.org/10.1093/jnci/djh305] [PMID: 15547183] 
[152] 
De Milito, A.; Iessi, E.; Logozzi, M.; Lozupone, F.; Spada, M.; Marino, M.L.; Federici, C.; Perdicchio, M.; Matarrese, P.; Lugini, L.; Nils-son, A.; Fais, S. Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species. Cancer Res.,  2007, 67(11), 5408-5417.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4095] [PMID: 17545622] 
[153] 
Marino, M.; Fais, S.; Djavaheri-Mergny, M.; Villa, A.; Meschini, S.; Lozupone, F.; Venturi, G.; Della Mina, P.; Pattingre, S.; Rivoltini, L. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells. Cell Death Dis.,  2010, 1(10), e87.
[http://dx.doi.org/10.1038/cddis.2010.67] 
[154] 
De Milito, A.; Canese, R.; Marino, M.L.; Borghi, M.; Iero, M.; Villa, A.; Venturi, G.; Lozupone, F.; Iessi, E.; Logozzi, M.; Della Mina, P.; Santinami, M.; Rodolfo, M.; Podo, F.; Rivoltini, L.; Fais, S. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int. J. Cancer,  2010, 127(1), 207-219.
[http://dx.doi.org/10.1002/ijc.25009] [PMID: 19876915] 
[155] 
Calcinotto, A.; Filipazzi, P.; Grioni, M.; Iero, M.; De Milito, A.; Ricupito, A.; Cova, A.; Canese, R.; Jachetti, E.; Rossetti, M.; Huber, V.; Parmiani, G.; Generoso, L.; Santinami, M.; Borghi, M.; Fais, S.; Bellone, M.; Rivoltini, L. Modulation of microenvironment acidity revers-es anergy in human and murine tumor-infiltrating T lymphocytes. Cancer Res.,  2012, 72(11), 2746-2756.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1272] [PMID: 22593198] 
[156] 
Wang, B-Y.; Zhang, J.; Wang, J-L.; Sun, S.; Wang, Z-H.; Wang, L-P.; Zhang, Q-L.; Lv, F-F.; Cao, E-Y.; Shao, Z-M.; Fais, S.; Hu, X.C. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J. Exp. Clin. Cancer Res.,  2015, 34(1), 85.
[http://dx.doi.org/10.1186/s13046-015-0194-x] [PMID: 26297142] 
[157] 
Perut, F.; Avnet, S.; Fotia, C.; Baglìo, S.R.; Salerno, M.; Hosogi, S.; Kusuzaki, K.; Baldini, N. V-ATPase as an effective therapeutic target for sarcomas. Exp. Cell Res.,  2014, 320(1), 21-32.
[http://dx.doi.org/10.1016/j.yexcr.2013.10.011] [PMID: 24416789] 
[158] 
Falk, G.W.; Buttar, N.S.; Foster, N.R.; Ziegler, K.L.A.; DeMars, C.J.; Romero, Y.; Marcon, N.E.; Schnell, T.; Corley, D.A.; Sharma, P. A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett’s esophagus. Gastroenterology,  2012, 143(4), 917-926.
[http://dx.doi.org/10.1053/j.gastro.2012.06.044] 
[159] 
Avnet, S.; Di Pompo, G.; Lemma, S.; Salerno, M.; Perut, F.; Bonuccelli, G.; Granchi, D.; Zini, N.; Baldini, N. V-ATPase is a candidate therapeutic target for Ewing sarcoma. Biochim. Biophys. Acta,  2013, 1832(8), 1105-1116.
[http://dx.doi.org/10.1016/j.bbadis.2013.04.003] 
[160] 
Udelnow, A.; Kreyes, A.; Ellinger, S.; Landfester, K.; Walther, P.; Klapperstueck, T.; Wohlrab, J.; Henne-Bruns, D.; Knippschild, U.; Würl, P. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One,  2011, 6(5), e20143.
[http://dx.doi.org/10.1371/journal.pone.0020143] [PMID: 21629657] 
[161] 
Vishvakarma, N.K.; Singh, S.M. Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host: Implication in antitumor activation of tumor-associated macrophages. Immunol. Lett.,  2010, 134(1), 83-92.
[http://dx.doi.org/10.1016/j.imlet.2010.09.002] [PMID: 20837061] 
[162] 
Riemann, A.; Güttler, A.; Haupt, V.; Wichmann, H.; Reime, S.; Bache, M.; Vordermark, D.; Thews, O. Inhibition of carbonic anhydrase IX by ureidosulfonamide inhibitor U104 reduces prostate cancer cell growth, but does not modulate daunorubicin or cisplatin cytotoxicity. Oncol. Res.,  2018, 26(2), 191-200.
[http://dx.doi.org/10.3727/096504017X14965111926391] [PMID: 28631600] 
[163] 
Peppicelli, S.; Andreucci, E.; Ruzzolini, J.; Bianchini, F.; Nediani, C.; Supuran, C.T.; Calorini, L. The carbonic anhydrase IX inhibitor SLC-0111 as emerging agent against the mesenchymal stem cell-derived pro-survival effects on melanoma cells. J. Enzyme Inhib. Med. Chem.,  2020, 35(1), 1185-1193.
[http://dx.doi.org/10.1080/14756366.2020.1764549] [PMID: 32396749] 
[164] 
Chafe, S.C.; McDonald, P.C.; Saberi, S.; Nemirovsky, O.; Venkateswaran, G.; Burugu, S.; Gao, D.; Delaidelli, A.; Kyle, A.H.; Baker, J.H.E.; Gillespie, J.A.; Bashashati, A.; Minchinton, A.I.; Zhou, Y.; Shah, S.P.; Dedhar, S. Targeting hypoxia-induced carbonic anhydrase IX enhances immune-checkpoint blockade locally and systemically. Cancer Immunol. Res.,  2019, 7(7), 1064-1078.
[http://dx.doi.org/10.1158/2326-6066.CIR-18-0657] [PMID: 31088846] 
[165] 
Lou, Y.; McDonald, P.C.; Oloumi, A.; Chia, S.; Ostlund, C.; Ahmadi, A.; Kyle, A.; Auf dem Keller, U.; Leung, S.; Huntsman, D.; Clarke, B.; Sutherland, B.W.; Waterhouse, D.; Bally, M.; Roskelley, C.; Overall, C.M.; Minchinton, A.; Pacchiano, F.; Carta, F.; Scozzafava, A.; Touisni, N.; Winum, J.Y.; Supuran, C.T.; Dedhar, S. Targeting tumor hypoxia: Suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res.,  2011, 71(9), 3364-3376.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4261] [PMID: 21415165] 
[166] 
Lock, F.E.; McDonald, P.C.; Lou, Y.; Serrano, I.; Chafe, S.C.; Ostlund, C.; Aparicio, S.; Winum, J-Y.; Supuran, C.T.; Dedhar, S. Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche. Oncogene,  2013, 32(44), 5210-5219.
[http://dx.doi.org/10.1038/onc.2012.550] [PMID: 23208505] 
[167] 
Hedlund, E.E.; McDonald, P.C.; Nemirovsky, O.; Awrey, S.; Jensen, L.D.E.; Dedhar, S. Harnessing induced essentiality: Targeting carbon-ic anhydrase IX and angiogenesis reduces lung metastasis of triple negative breast cancer xenografts. Cancers (Basel),  2019, 11(7), 1002.
[http://dx.doi.org/10.3390/cancers11071002] [PMID: 31319613] 
[168] 
McDonald, P.C.; Chafe, S.C.; Brown, W.S.; Saberi, S.; Swayampakula, M.; Venkateswaran, G.; Nemirovsky, O.; Gillespie, J.A.; Karasin-ska, J.M.; Kalloger, S.E.; Supuran, C.T.; Schaeffer, D.F.; Bashashati, A.; Shah, S.P.; Topham, J.T.; Yapp, D.T.; Li, J.; Renouf, D.J.; Stan-ger, B.Z.; Dedhar, S. Regulation of pH by carbonic anhydrase 9 mediates survival of pancreatic cancer cells with activated KRAS in re-sponse to hypoxia. Gastroenterology,  2019, 157(3), 823-837.
[http://dx.doi.org/10.1053/j.gastro.2019.05.004] [PMID: 31078621] 
[169] 
Boyd, N.H.; Walker, K.; Fried, J.; Hackney, J.R.; McDonald, P.C.; Benavides, G.A.; Spina, R.; Audia, A.; Scott, S.E.; Libby, C.J.; Tran, A.N.; Bevensee, M.O.; Griguer, C.; Nozell, S.; Gillespie, G.Y.; Nabors, B.; Bhat, K.P.; Bar, E.E.; Darley-Usmar, V.; Xu, B.; Gordon, E.; Cooper, S.J.; Dedhar, S.; Hjelmeland, A.B. Addition of carbonic anhydrase 9 inhibitor SLC-0111 to temozolomide treatment delays glio-blastoma growth in vivo. JCI Insight,  2017, 2(24), 92928.
[http://dx.doi.org/10.1172/jci.insight.92928] [PMID: 29263302] 
Rights & Permissions Print Cite
Article Metrics
16
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1568009622666220401093316	Print ISSN 1568-0096
Publisher Name Bentham Science Publisher	Online ISSN 1873-5576
Current Cancer Drug Targets

Pharmacological Inhibition of Exosome Machinery: An Emerging Prospect in Cancer Therapeutics

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
