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Current Cancer Drug Targets

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

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Mini-Review Article

The Therapeutic Potential of Targeting Autophagy in the Treatment of Cancer

Author(s): Negin Chaeichi-Tehrani, Gordon A. Ferns, Seyed Mahdi Hassanian, Majid Khazaei* and Amir Avan

Volume 21, Issue 9, 2021

Published on: 01 June, 2021

Page: [725 - 736] Pages: 12

DOI: 10.2174/1568009621666210601113144

Price: $65

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Abstract

Autophagy is a mechanism by which unwanted cellular components are degraded through a pathway that involves the lysosomes and contributes to several pathological conditions such as cancer. Gastrointestinal cancers affect the digestive organs from the esophagus to the anus and are among the most commonly diagnosed cancers globally. The modulation of autophagy using pharmacologic agents offers a great potential for cancer therapy. In this review, some commonly used compounds, together with their molecular target and the mechanism through which they stimulate or block the autophagy pathway, as well as their therapeutic benefit in treating patients with gastrointestinal cancers, are summarized.

Keywords: Autophagy, lysosomes, pharmacologic agents, gastrointestinal cancers, therapeutic potential, chemotherapeutic drug.

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[1]
Taniguchi, H.; Moriya, C.; Igarashi, H.; Saitoh, A.; Yamamoto, H.; Adachi, Y.; Imai, K. Cancer stem cells in human gastrointestinal cancer. Cancer Sci., 2016, 107(11), 1556-1562.
[http://dx.doi.org/10.1111/cas.13069] [PMID: 27575869]
[2]
Jiang, P.; Mizushima, N. Autophagy and human diseases. Cell Res., 2014, 24(1), 69-79.
[http://dx.doi.org/10.1038/cr.2013.161] [PMID: 24323045]
[3]
Koustas, E.; Sarantis, P.; Kyriakopoulou, G.; Papavassiliou, A.G.; Karamouzis, M.V. The interplay of autophagy and tumor microenvironment in colorectal cancer-ways of enhancing immunotherapy action. Cancers (Basel), 2019, 11(4), E533.
[http://dx.doi.org/10.3390/cancers11040533] [PMID: 31013961]
[4]
Li, F.; Guo, H.; Yang, Y.; Feng, M.; Liu, B.; Ren, X.; Zhou, H. Autophagy modulation in bladder cancer development and treatment (Review). Oncol. Rep., 2019, 42(5), 1647-1655.
[http://dx.doi.org/10.3892/or.2019.7286] [PMID: 31436298]
[5]
Folkerts, H.; Hilgendorf, S.; Vellenga, E.; Bremer, E.; Wiersma, V.R. The multifaceted role of autophagy in cancer and the microenvironment. Med. Res. Rev., 2019, 39(2), 517-560.
[http://dx.doi.org/10.1002/med.21531] [PMID: 30302772]
[6]
Barth, S.; Glick, D.; Macleod, K.F. Autophagy: assays and artifacts. J. Pathol., 2010, 221(2), 117-124.
[http://dx.doi.org/10.1002/path.2694] [PMID: 20225337]
[7]
Limpert, A.S.; Lambert, L.J.; Bakas, N.A.; Bata, N.; Brun, S.N.; Shaw, R.J.; Cosford, N.D.P. Autophagy in cancer: regulation by small molecules. Trends Pharmacol. Sci., 2018, 39(12), 1021-1032.
[http://dx.doi.org/10.1016/j.tips.2018.10.004] [PMID: 30454769]
[8]
Heckmann, B.L.; Yang, X.; Zhang, X.; Liu, J. The autophagic inhibitor 3-methyladenine potently stimulates PKA-dependent lipolysis in adipocytes. Br. J. Pharmacol., 2013, 168(1), 163-171.
[http://dx.doi.org/10.1111/j.1476-5381.2012.02110.x] [PMID: 22817685]
[9]
Pasquier, B. Autophagy inhibitors. Cell. Mol. Life Sci., 2016, 73(5), 985-1001.
[http://dx.doi.org/10.1007/s00018-015-2104-y] [PMID: 26658914]
[10]
Yang, Y.P.; Hu, L.F.; Zheng, H.F.; Mao, C.J.; Hu, W.D.; Xiong, K.P.; Wang, F.; Liu, C.F. Application and interpretation of current autophagy inhibitors and activators. Acta Pharmacol. Sin., 2013, 34(5), 625-635.
[http://dx.doi.org/10.1038/aps.2013.5] [PMID: 23524572]
[11]
Pesce, E.; Sondo, E.; Ferrera, L.; Tomati, V.; Caci, E.; Scudieri, P.; Musante, I.; Renda, M.; Baatallah, N.; Servel, N.; Hinzpeter, A.; di Bernardo, D.; Pedemonte, N.; Galietta, L.J.V. The autophagy inhibitor spautin-1 antagonizes rescue of mutant CFTR through an autophagy-independent and USP13-mediated mechanism. Front. Pharmacol., 2018, 9, 1464.
[http://dx.doi.org/10.3389/fphar.2018.01464] [PMID: 30618756]
[12]
Ronan, B.; Flamand, O.; Vescovi, L.; Dureuil, C.; Durand, L.; Fassy, F.; Bachelot, M.F.; Lamberton, A.; Mathieu, M.; Bertrand, T.; Marquette, J.P.; El-Ahmad, Y.; Filoche-Romme, B.; Schio, L.; Garcia-Echeverria, C.; Goulaouic, H.; Pasquier, B. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat. Chem. Biol., 2014, 10(12), 1013-1019.
[http://dx.doi.org/10.1038/nchembio.1681] [PMID: 25326666]
[13]
Egan, D.F.; Chun, M.G.; Vamos, M.; Zou, H.; Rong, J.; Miller, C.J.; Lou, H.J.; Raveendra-Panickar, D.; Yang, C.C.; Sheffler, D.J.; Teriete, P.; Asara, J.M.; Turk, B.E.; Cosford, N.D.; Shaw, R.J. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol. Cell, 2015, 59(2), 285-297.
[http://dx.doi.org/10.1016/j.molcel.2015.05.031] [PMID: 26118643]
[14]
Mauvezin, C.; Neufeld, T.P. Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. Autophagy, 2015, 11(8), 1437-1438.
[http://dx.doi.org/10.1080/15548627.2015.1066957] [PMID: 26156798]
[15]
Al-Bari, A.A. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J. Antimicrob. Chemother., 2015, 70(6), 1608-1621.
[http://dx.doi.org/10.1093/jac/dkv018] [PMID: 25693996]
[16]
Mauthe, M.; Orhon, I.; Rocchi, C.; Zhou, X.; Luhr, M.; Hijlkema, K.J.; Coppes, R.P.; Engedal, N.; Mari, M.; Reggiori, F. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy, 2018, 14(8), 1435-1455.
[http://dx.doi.org/10.1080/15548627.2018.1474314] [PMID: 29940786]
[17]
Ben-Zvi, I.; Kivity, S.; Langevitz, P.; Shoenfeld, Y. Hydroxychloroquine: from malaria to autoimmunity. Clin. Rev. Allergy Immunol., 2012, 42(2), 145-153.
[http://dx.doi.org/10.1007/s12016-010-8243-x] [PMID: 21221847]
[18]
Dielschneider, R.F.; Henson, E.S.; Gibson, S.B. Lysosomes as oxidative targets for cancer therapy. Oxid. Med. Cell. Longev., 2017, 2017, 3749157.
[http://dx.doi.org/10.1155/2017/3749157] [PMID: 28757908]
[19]
Verbaanderd, C.; Maes, H.; Schaaf, M.B.; Sukhatme, V.P.; Pantziarka, P.; Sukhatme, V.; Agostinis, P.; Bouche, G. Repurposing drugs in oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience, 2017, 11, 781.
[http://dx.doi.org/10.3332/ecancer.2017.781] [PMID: 29225688]
[20]
McAfee, Q.; Zhang, Z.; Samanta, A.; Levi, S.M.; Ma, X.H.; Piao, S.; Lynch, J.P.; Uehara, T.; Sepulveda, A.R.; Davis, L.E.; Winkler, J.D.; Amaravadi, R.K. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc. Natl. Acad. Sci. USA, 2012, 109(21), 8253-8258.
[http://dx.doi.org/10.1073/pnas.1118193109] [PMID: 22566612]
[21]
Motoi, Y.; Shimada, K.; Ishiguro, K.; Hattori, N. Lithium and autophagy. ACS Chem. Neurosci., 2014, 5(6), 434-442.
[http://dx.doi.org/10.1021/cn500056q] [PMID: 24738557]
[22]
Vakifahmetoglu-Norberg, H.; Xia, H.G.; Yuan, J. Pharmacologic agents targeting autophagy. J. Clin. Invest., 2015, 125(1), 5-13.
[http://dx.doi.org/10.1172/JCI73937] [PMID: 25654545]
[23]
Kondratskyi, A.; Kondratska, K.; Skryma, R.; Klionsky, D.J.; Prevarskaya, N. Ion channels in the regulation of autophagy. Autophagy, 2018, 14(1), 3-21.
[http://dx.doi.org/10.1080/15548627.2017.1384887] [PMID: 28980859]
[24]
Wu, Y.C.; Wu, W.K.; Li, Y.; Yu, L.; Li, Z.J.; Wong, C.C.; Li, H.T.; Sung, J.J.; Cho, C.H. Inhibition of macroautophagy by bafilomycin A1 lowers proliferation and induces apoptosis in colon cancer cells. Biochem. Biophys. Res. Commun., 2009, 382(2), 451-456.
[http://dx.doi.org/10.1016/j.bbrc.2009.03.051] [PMID: 19289106]
[25]
Li, L.Q.; Xie, W.J.; Pan, D.; Chen, H.; Zhang, L. Inhibition of autophagy by bafilomycin A1 promotes chemosensitivity of gastric cancer cells. Tumour Biol., 2016, 37(1), 653-659.
[http://dx.doi.org/10.1007/s13277-015-3842-z] [PMID: 26242265]
[26]
Qiao, X.; Wang, X.; Shang, Y.; Li, Y.; Chen, S.Z. Azithromycin enhances anticancer activity of TRAIL by inhibiting autophagy and up-regulating the protein levels of DR4/5 in colon cancer cells in vitro and in vivo. Cancer Commun (Lond), 2018, 38(1), 43.
[http://dx.doi.org/10.1186/s40880-018-0309-9] [PMID: 29970185]
[27]
Dong, Y.; Wu, Y.; Zhao, G.L.; Ye, Z.Y.; Xing, C.G.; Yang, X.D. Inhibition of autophagy by 3-MA promotes hypoxia-induced apoptosis in human colorectal cancer cells. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(3), 1047-1054.
[PMID: 30779071]
[28]
Mukubou, H.; Tsujimura, T.; Sasaki, R.; Ku, Y. The role of autophagy in the treatment of pancreatic cancer with gemcitabine and ionizing radiation. Int. J. Oncol., 2010, 37(4), 821-828.
[http://dx.doi.org/10.3892/ijo-00000732] [PMID: 20811703]
[29]
He, X.X.; Huang, C.K.; Xie, B.S. Autophagy inhibition enhanced 5-FU-induced cell death in human gastric carcinoma BGC-823 cells. Mol. Med. Rep., 2018, 17(5), 6768-6776.
[http://dx.doi.org/10.3892/mmr.2018.8661] [PMID: 29512733]
[30]
Sasaki, K.; Tsuno, N.H.; Sunami, E.; Tsurita, G.; Kawai, K.; Okaji, Y.; Nishikawa, T.; Shuno, Y.; Hongo, K.; Hiyoshi, M.; Kaneko, M.; Kitayama, J.; Takahashi, K.; Nagawa, H. Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells. BMC Cancer, 2010, 10, 370.
[http://dx.doi.org/10.1186/1471-2407-10-370] [PMID: 20630104]
[31]
Song, Y.J.; Zhang, S.S.; Guo, X.L.; Sun, K.; Han, Z.P.; Li, R.; Zhao, Q.D.; Deng, W.J.; Xie, X.Q.; Zhang, J.W.; Wu, M.C.; Wei, L.X. Autophagy contributes to the survival of CD133+ liver cancer stem cells in the hypoxic and nutrient-deprived tumor microenvironment. Cancer Lett., 2013, 339(1), 70-81.
[http://dx.doi.org/10.1016/j.canlet.2013.07.021] [PMID: 23879969]
[32]
Hashimoto, D.; Bläuer, M.; Hirota, M.; Ikonen, N.H.; Sand, J.; Laukkarinen, J. Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs. Eur. J. Cancer, 2014, 50(7), 1382-1390.
[http://dx.doi.org/10.1016/j.ejca.2014.01.011] [PMID: 24503026]
[33]
Dong, X.; Wang, Y.; Zhou, Y.; Wen, J.; Wang, S.; Shen, L. Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatin via autophagy. Cell Death Discov., 2016, 2, 16087.
[http://dx.doi.org/10.1038/cddiscovery.2016.87] [PMID: 27867537]
[34]
Cai, Q.; Wang, X.; Wang, S.; Jin, L.; Ding, J.; Zhou, D.; Ma, F. Gallbladder cancer progression is reversed by nanomaterial-induced photothermal therapy in combination with chemotherapy and autophagy inhibition. Int. J. Nanomedicine, 2020, 15, 253-262.
[http://dx.doi.org/10.2147/IJN.S231289] [PMID: 32021178]
[35]
Liang, X.; Tang, J.; Liang, Y.; Jin, R.; Cai, X. Suppression of autophagy by chloroquine sensitizes 5-fluorouracil-mediated cell death in gallbladder carcinoma cells. Cell Biosci., 2014, 4(1), 10.
[http://dx.doi.org/10.1186/2045-3701-4-10] [PMID: 24581180]
[36]
Amaravadi, R.K.; Winkler, J.D. Lys05: a new lysosomal autophagy inhibitor. Autophagy, 2012, 8(9), 1383-1384.
[http://dx.doi.org/10.4161/auto.20958] [PMID: 22878685]
[37]
Scott, A.J.; Arcaroli, J.J.; Bagby, S.M.; Yahn, R.; Huber, K.M.; Serkova, N.J.; Nguyen, A.; Kim, J.; Thorburn, A.; Vogel, J.; Quackenbush, K.S.; Capasso, A.; Schreiber, A.; Blatchford, P.; Klauck, P.J.; Pitts, T.M.; Eckhardt, S.G.; Messersmith, W.A. Cabozantinib exhibits potent antitumor activity in colorectal cancer patient-derived tumor xenograft models via autophagy and signaling mechanisms. Mol. Cancer Ther., 2018, 17(10), 2112-2122.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0131] [PMID: 30026382]
[38]
Gil-Ad, I.; Zolokov, A.; Lomnitski, L.; Taler, M.; Bar, M.; Luria, D.; Ram, E.; Weizman, A. Evaluation of the potential anti-cancer activity of the antidepressant sertraline in human colon cancer cell lines and in colorectal cancer-xenografted mice. Int. J. Oncol., 2008, 33(2), 277-286.
[http://dx.doi.org/10.3892/ijo_00000007] [PMID: 18636148]
[39]
Park, W.H.; Kim, E.S.; Jung, C.W.; Kim, B.K.; Lee, Y.Y. Monensin-mediated growth inhibition of SNU-C1 colon cancer cells via cell cycle arrest and apoptosis. Int. J. Oncol., 2003, 22(2), 377-382.
[http://dx.doi.org/10.3892/ijo.22.2.377] [PMID: 12527937]
[40]
Wang, X.; Wu, X.; Zhang, Z.; Ma, C.; Wu, T.; Tang, S.; Zeng, Z.; Huang, S.; Gong, C.; Yuan, C.; Zhang, L.; Feng, Y.; Huang, B.; Liu, W.; Zhang, B.; Shen, Y.; Luo, W.; Wang, X.; Liu, B.; Lei, Y.; Ye, Z.; Zhao, L.; Cao, D.; Yang, L.; Chen, X.; Haydon, R.C.; Luu, H.H.; Peng, B.; Liu, X.; He, T.C. Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway. Sci. Rep., 2018, 8(1), 17914.
[http://dx.doi.org/10.1038/s41598-018-36214-5] [PMID: 30559409]
[41]
Vakifahmetoglu-Norberg, H.; Kim, M.; Xia, H.G.; Iwanicki, M.P.; Ofengeim, D.; Coloff, J.L.; Pan, L.; Ince, T.A.; Kroemer, G.; Brugge, J.S.; Yuan, J. Chaperone-mediated autophagy degrades mutant p53. Genes Dev., 2013, 27(15), 1718-1730.
[http://dx.doi.org/10.1101/gad.220897.113] [PMID: 23913924]
[42]
Zhu, M.M.; Tong, J.L.; Xu, Q.; Nie, F.; Xu, X.T.; Xiao, S.D.; Ran, Z.H. Increased JNK1 signaling pathway is responsible for ABCG2-mediated multidrug resistance in human colon cancer. PLoS One, 2012, 7(8), e41763.
[http://dx.doi.org/10.1371/journal.pone.0041763] [PMID: 22870247]
[43]
Zhou, G.; Yang, J.; Song, P. Correlation of ERK/MAPK signaling pathway with proliferation and apoptosis of colon cancer cells. Oncol. Lett., 2019, 17(2), 2266-2270.
[http://dx.doi.org/10.3892/ol.2018.9857] [PMID: 30675292]
[44]
Wang, Q.; Li, N.; Wang, X.; Kim, M.M.; Evers, B.M. Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3′-kinase inhibition in the KM20 human colon cancer cell line. Clin. Cancer Res., 2002, 8(6), 1940-1947.
[PMID: 12060639]
[45]
Ng, S.S.W.; Tsao, M.S.; Nicklee, T.; Hedley, D.W. Wortmannin inhibits pkb/akt phosphorylation and promotes gemcitabine antitumor activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clin. Cancer Res., 2001, 7(10), 3269-3275.
[PMID: 11595724]
[46]
Li, B.; Li, J.; Xu, W.W.; Guan, X.Y.; Qin, Y.R.; Zhang, L.Y.; Law, S.; Tsao, S.W.; Cheung, A.L. Suppression of esophageal tumor growth and chemoresistance by directly targeting the PI3K/AKT pathway. Oncotarget, 2014, 5(22), 11576-11587.
[http://dx.doi.org/10.18632/oncotarget.2596] [PMID: 25344912]
[47]
Semba, S.; Itoh, N.; Ito, M.; Harada, M.; Yamakawa, M. The in vitro and in vivo effects of 2-(4-morpholinyl)-8-phenylchromone (LY294002), a specific inhibitor of phosphatidylinositol 3′-kinase, in human colon cancer cells. Clin. Cancer Res., 2002, 8(6), 1957-1963.
[PMID: 12060641]
[48]
Fujiwara, M.; Izuishi, K.; Sano, T.; Hossain, M.A.; Kimura, S.; Masaki, T.; Suzuki, Y. Modulating effect of the PI3-kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells. J. Exp. Clin. Cancer Res., 2008, 27, 76.
[http://dx.doi.org/10.1186/1756-9966-27-76] [PMID: 19032736]
[49]
Yang, S.Y.; Miah, A.; Sales, K.M.; Fuller, B.; Seifalian, A.M.; Winslet, M. Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment. Int. J. Oncol., 2011, 38(6), 1695-1702.
[http://dx.doi.org/10.3892/ijo.2011.982] [PMID: 21424124]
[50]
Wei, R.; Xiao, Y.; Song, Y.; Yuan, H.; Luo, J.; Xu, W. FAT4 regulates the EMT and autophagy in colorectal cancer cells in part via the PI3K-AKT signaling axis. J. Exp. Clin. Cancer Res., 2019, 38(1), 112.
[http://dx.doi.org/10.1186/s13046-019-1043-0] [PMID: 30832706]
[51]
Xu, N.; Zhang, J.; Shen, C.; Luo, Y.; Xia, L.; Xue, F.; Xia, Q. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. Biochem. Biophys. Res. Commun., 2012, 423(4), 826-831.
[http://dx.doi.org/10.1016/j.bbrc.2012.06.048] [PMID: 22713463]
[52]
Chang, Y.; Yan, W.; He, X.; Zhang, L.; Li, C.; Huang, H.; Nace, G.; Geller, D.A.; Lin, J.; Tsung, A. miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology, 2012, 143(1), 177-87.e8.
[http://dx.doi.org/10.1053/j.gastro.2012.04.009] [PMID: 22504094]
[53]
Xu, Y.; An, Y.; Wang, Y.; Zhang, C.; Zhang, H.; Huang, C.; Jiang, H.; Wang, X.; Li, X. miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells. Oncol. Rep., 2013, 29(5), 2019-2024.
[http://dx.doi.org/10.3892/or.2013.2338] [PMID: 23483142]
[54]
He, C.; Dong, X.; Zhai, B.; Jiang, X.; Dong, D.; Li, B.; Jiang, H.; Xu, S.; Sun, X. MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Oncotarget, 2015, 6(30), 28867-28881.
[http://dx.doi.org/10.18632/oncotarget.4814] [PMID: 26311740]
[55]
Timme, C.R.; Gruidl, M.; Yeatman, T.J. Gamma-secretase inhibition attenuates oxaliplatin-induced apoptosis through increased Mcl-1 and/or Bcl-xL in human colon cancer cells. Apoptosis, 2013, 18(10), 1163-1174.
[http://dx.doi.org/10.1007/s10495-013-0883-x] [PMID: 23887890]
[56]
Law, B.Y.K.; Chan, W.K.; Xu, S.W.; Wang, J.R.; Bai, L.P.; Liu, L.; Wong, V.K. Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells. Sci. Rep., 2014, 4, 5510.
[http://dx.doi.org/10.1038/srep05510] [PMID: 24981420]
[57]
Rattanawong, A.; Payon, V.; Limpanasittikul, W.; Boonkrai, C.; Mutirangura, A.; Wonganan, P. Cepharanthine exhibits a potent anticancer activity in p53-mutated colorectal cancer cells through upregulation of p21Waf1/Cip1. Oncol. Rep., 2018, 39(1), 227-238.
[http://dx.doi.org/10.3892/or.2017.6084] [PMID: 29138869]
[58]
Song, X.; Zhu, S.; Chen, P.; Hou, W.; Wen, Q.; Liu, J.; Xie, Y.; Liu, J.; Klionsky, D.J.; Kroemer, G.; Lotze, M.T.; Zeh, H.J.; Kang, R.; Tang, D. AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc- activity. Curr. Biol., 2018, 28(15), 2388-2399.e5.
[http://dx.doi.org/10.1016/j.cub.2018.05.094] [PMID: 30057310]
[59]
Tang, J.Y.; Dai, T.; Zhang, H.; Xiong, W.J.; Xu, M.Z.; Wang, X.J.; Tang, Q.H.; Chen, B.; Xu, M. GDC-0980-induced apoptosis is enhanced by autophagy inhibition in human pancreatic cancer cells. Biochem. Biophys. Res. Commun., 2014, 453(3), 533-538.
[http://dx.doi.org/10.1016/j.bbrc.2014.09.115] [PMID: 25285629]
[60]
Floris, G.; Wozniak, A.; Sciot, R.; Li, H.; Friedman, L.; Van Looy, T.; Wellens, J.; Vermaelen, P.; Deroose, C.M.; Fletcher, J.A.; Debiec-Rychter, M.; Schöffski, P. A potent combination of the novel PI3K Inhibitor, GDC-0941, with imatinib in gastrointestinal stromal tumor xenografts: long-lasting responses after treatment withdrawal. Clin. Cancer Res., 2013, 19(3), 620-630.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2853] [PMID: 23231951]
[61]
Patil, S.P.; Pacitti, M.F.; Gilroy, K.S.; Ruggiero, J.C.; Griffin, J.D.; Butera, J.J.; Notarfrancesco, J.M.; Tran, S.; Stoddart, J.W. Identification of antipsychotic drug fluspirilene as a potential p53-MDM2 inhibitor: a combined computational and experimental study. J. Comput. Aided Mol. Des., 2015, 29(2), 155-163.
[http://dx.doi.org/10.1007/s10822-014-9811-6] [PMID: 25377899]
[62]
Bearzatto, A. Nimodipine as a modulator of resistance to doxorubicin in human colon-adenocarcinoma cells: A comparative study with verapamil. Int. J. Oncol., 1996.
[http://dx.doi.org/10.3892/ijo.9.1.57]
[63]
Huang, S.T.; Hsu, W.F.; Huang, H.S.; Yen, J.H.; Lin, M.C.; Peng, C.Y.; Yen, H.R. Improved survival in hepatocellular carcinoma patients with cardiac arrhythmia by amiodarone treatment through autophagy. Int. J. Mol. Sci., 2019, 20(16), E3978.
[http://dx.doi.org/10.3390/ijms20163978] [PMID: 31443312]
[64]
Li, X.; He, S.; Ma, B. Autophagy and autophagy-related proteins in cancer. Mol. Cancer, 2020, 19(1), 12.
[http://dx.doi.org/10.1186/s12943-020-1138-4] [PMID: 31969156]
[65]
Huang, T.; Song, X.; Yang, Y.; Wan, X.; Alvarez, A.A.; Sastry, N.; Feng, H.; Hu, B.; Cheng, S.Y. Autophagy and hallmarks of cancer. Crit. Rev. Oncog., 2018, 23(5-6), 247-267.
[http://dx.doi.org/10.1615/CritRevOncog.2018027913] [PMID: 30311559]
[66]
Burada, F.; Nicoli, E.R.; Ciurea, M.E.; Uscatu, D.C.; Ioana, M.; Gheonea, D.I. Autophagy in colorectal cancer: An important switch from physiology to pathology. World J. Gastrointest. Oncol., 2015, 7(11), 271-284.
[http://dx.doi.org/10.4251/wjgo.v7.i11.271] [PMID: 26600927]
[67]
Mahalingam, D.; Mita, M.; Sarantopoulos, J.; Wood, L.; Amaravadi, R.K.; Davis, L.E.; Mita, A.C.; Curiel, T.J.; Espitia, C.M.; Nawrocki, S.T.; Giles, F.J.; Carew, J.S. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy, 2014, 10(8), 1403-1414.
[http://dx.doi.org/10.4161/auto.29231] [PMID: 24991835]
[68]
Yang, A.; Herter-Sprie, G.; Zhang, H.; Lin, E.Y.; Biancur, D.; Wang, X.; Deng, J.; Hai, J.; Yang, S.; Wong, K.K.; Kimmelman, A.C. Autophagy sustains pancreatic cancer growth through both cell-autonomous and nonautonomous mechanisms. Cancer Discov., 2018, 8(3), 276-287.
[http://dx.doi.org/10.1158/2159-8290.CD-17-0952] [PMID: 29317452]
[69]
Yang, A.; Kimmelman, A.C. Inhibition of autophagy attenuates pancreatic cancer growth independent of TP53/TRP53 status. Autophagy, 2014, 10(9), 1683-1684.
[http://dx.doi.org/10.4161/auto.29961] [PMID: 25046107]
[70]
Donohue, E.; Thomas, A.; Maurer, N.; Manisali, I.; Zeisser-Labouebe, M.; Zisman, N.; Anderson, H.J.; Ng, S.S.; Webb, M.; Bally, M.; Roberge, M. The autophagy inhibitor verteporfin moderately enhances the antitumor activity of gemcitabine in a pancreatic ductal adenocarcinoma model. J. Cancer, 2013, 4(7), 585-596.
[http://dx.doi.org/10.7150/jca.7030] [PMID: 24069069]
[71]
Huggett, M.T.; Jermyn, M.; Gillams, A.; Illing, R.; Mosse, S.; Novelli, M.; Kent, E.; Bown, S.G.; Hasan, T.; Pogue, B.W.; Pereira, S.P. Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer. Br. J. Cancer, 2014, 110(7), 1698-1704.
[http://dx.doi.org/10.1038/bjc.2014.95] [PMID: 24569464]
[72]
Chak, A.; Buttar, N.S.; Foster, N.R.; Seisler, D.K.; Marcon, N.E.; Schoen, R.; Cruz-Correa, M.R.; Falk, G.W.; Sharma, P.; Hur, C.; Katzka, D.A.; Rodriguez, L.M.; Richmond, E.; Sharma, A.N.; Smyrk, T.C.; Mandrekar, S.J.; Limburg, P.J. Metformin does not reduce markers of cell proliferation in esophageal tissues of patients with Barrett’s esophagus. Clin. Gastroenterol. Hepatol., 2015, 13(4), 665-72.e1, 4.
[http://dx.doi.org/10.1016/j.cgh.2014.08.040] [PMID: 25218668]
[73]
Akkoç, Y.; Gözüaçık, D. Autophagy and liver cancer. Turk. J. Gastroenterol., 2018, 29(3), 270-282.
[http://dx.doi.org/10.5152/tjg.2018.150318] [PMID: 29755011]
[74]
Manogaran, P.; Beeraka, N.M.; Padma, V.V. The cytoprotective and anti-cancer potential of bisbenzylisoquinoline alkaloids from Nelumbo nucifera. Curr. Top. Med. Chem., 2019, 19(32), 2940-2957.
[http://dx.doi.org/10.2174/1568026619666191116160908] [PMID: 31738137]
[75]
Gao, J.J.; Shi, Z.Y.; Xia, J.F.; Inagaki, Y.; Tang, W. Sorafenib-based combined molecule targeting in treatment of hepatocellular carcinoma. World J. Gastroenterol., 2015, 21(42), 12059-12070.
[http://dx.doi.org/10.3748/wjg.v21.i42.12059] [PMID: 26576091]
[76]
Wainberg, Z.A.; Soares, H.P.; Patel, R.; DiCarlo, B.; Park, D.J.; Liem, A.; Wang, H.J.; Yonemoto, L.; Martinez, D.; Laux, I.; Brennan, M.; Hecht, J.R. Phase II trial of everolimus in patients with refractory metastatic adenocarcinoma of the esophagus, gastroesophageal junction and stomach: possible role for predictive biomarkers. Cancer Chemother. Pharmacol., 2015, 76(1), 61-67.
[http://dx.doi.org/10.1007/s00280-015-2744-5] [PMID: 25969130]
[77]
Hundal, R.; Shaffer, E.A. Gallbladder cancer: epidemiology and outcome. Clin. Epidemiol., 2014, 6, 99-109.
[http://dx.doi.org/10.2147/CLEP.S37357] [PMID: 24634588]

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