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Targeting Autophagy in Cancer Therapy pp 1–16Cite as

Autophagy as a Therapeutic Target in Cancer

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Part of the book series: Current Cancer Research ((CUCR))

Abstract

Autophagy is the process by which cellular material is delivered to the lysosome for degradation and recycling. Macroautophagy involves delivery of macromolecules and organelles to double membrane vesicles called autophagosomes that fuse with lysosomes leading to degradation of the contents of the autophagosomes. Chaperone-mediated autophagy involves direct recognition of specific proteins by chaperone complexes that then directly deliver the protein target to the lysosome. Microautophagy involves direct lysosomal capture of cytoplasmic material. Of these three types, macroautophagy is by far the most studied and is known to have multiple roles in cancer development, progression and response to therapy. This has led to autophagy being widely viewed as a potential therapeutic target in cancer. Important questions that must be answered include: Which tumors should or should not be treated by direct autophagy inhibition? And, what is the best way to target autophagy for cancer therapy? In this overview we summarize the background and some current ideas about the answers to such questions.

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References

  • Amaravadi, R. K., Yu, D., Lum, J. J., Bui, T., Christophorou, M. A., Evan, G. I., et al. (2007). Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. Journal of Clinical Investigation, 117, 326–336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arias, E., & Cuervo, A. M. (2011). Chaperone-mediated autophagy in protein quality control. Current Opinion in Cell Biology, 23, 184–189.

    Article  CAS  PubMed  Google Scholar 

  • Baginska, J., Viry, E., Berchem, G., Poli, A., Noman, M. Z., Van Moer, K., et al. (2013). Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia. Proceedings of the National Academy of Sciences of the United States of America, 110, 17450–17455.

    Google Scholar 

  • Bago, R., Malik, N., Munson, M. J., Prescott, A. R., Davies, P., Sommer, E., et al. (2014). Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. The Biochemical Journal, 463, 413–427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnard, R. A., Wittenburg, L. A., Amaravadi, R. K., Gustafson, D. L., Thorburn, A., & Thamm, D. H. (2014). Phase I clinical trial and pharmacodynamic evaluation of combination hydroxychloroquine and doxorubicin treatment in pet dogs treated for spontaneously occurring lymphoma. Autophagy, 10, 1415–1425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bursch, W., Ellinger, A., Kienzl, H., Torok, L., Pandey, S., Sikorska, M., et al. (1996). Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: The role of autophagy. Carcinogenesis, 17, 1595–1607.

    Article  CAS  PubMed  Google Scholar 

  • Chourasia, A. H., Tracy, K., Frankenberger, C., Boland, M. L., Sharifi, M. N., Drake, L. E., et al. (2015). Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis. EMBO Reports, 16, 1145–1163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dowdle, W. E., Nyfeler, B., Nagel, J., Elling, R. A., Liu, S., Triantafellow, E., et al. (2014). Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nature Cell Biology, 16(11), 1069–1079.

    Article  CAS  PubMed  Google Scholar 

  • Egan, D. F., Chun, M. G. H., Vamos, M., Zou, H., Rong, J., Miller, C. J., et al. (2015). Small Molecule Inhibition of the autophagy kinase ULK1 and Identification of ULK1 substrates. Molecular Cell, 59, 285–297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eng, C. H., Wang, Z., Tkach, D., Toral-Barza, L., Ugwonali, S., Liu, S., et al. (2016). Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proceedings of the National Academy of Sciences of the United States of America, 113, 182–187.

    Google Scholar 

  • Fitzwalter, B. E., & Thorburn, A. (2015). Recent insights into cell death and autophagy. The FEBS Journal, 282, 4279–4288.

    Article  CAS  PubMed  Google Scholar 

  • Galluzzi, L., Pietrocola, F., Pedro Bravo-San, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., et al. (2015). Autophagy in malignant transformation and cancer progression. The EMBO Journal, 34(7), 856–880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goodall, M. L., Wang, T., Martin, K. R., Kortus, M. G., Kauffman, A. L., Trent, J. M., et al. (2014). Development of potent autophagy inhibitors that sensitize oncogenic BRAF V600E mutant melanoma tumor cells to vemurafenib. Autophagy, 10, 1120–1136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gump, J. M., Staskiewicz, L., Morgan, M. J., Bamberg, A., Riches, D. W. H., & Thorburn, A. (2014). Autophagy variation within a cell population determines cell fate through selective degradation of Fap-1. Nature Cell Biology, 16, 47–54.

    Article  CAS  PubMed  Google Scholar 

  • Guo, J. Y., Chen, H.-Y., Mathew, R., Fan, J., Strohecker, A. M., Karsli-Uzunbas, G., et al. (2011). Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes and Development, 25, 460–470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo, J. Y., Karsli-Uzunbas, G., Mathew, R., Aisner, S. C., Kamphorst, J. J., Strohecker, A. M., et al. (2013a). Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes and Development, 27, 1447–1461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo, J. Y., Xia, B., & White, E. (2013b). Autophagy-mediated tumor promotion. Cell, 155, 1216–1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hippert, M. M., O’Toole, P. S., & Thorburn, A. (2006). Autophagy in cancer: Good, bad, or both? Cancer Research, 66, 9349–9351.

    Article  CAS  PubMed  Google Scholar 

  • Holohan, C., Van Schaeybroeck, S., Longley, D. B., & Johnston, P. G. (2013). Cancer drug resistance: An evolving paradigm. Nature Reviews Cancer, 13, 714–726.

    Article  CAS  PubMed  Google Scholar 

  • Huo, Y., Cai, H., Teplova, I., Bowman-Colin, C., Chen, G., Price, S., et al. (2013). Autophagy opposes p53-mediated tumor barrier to facilitate tumorigenesis in a model of PALB2-associated hereditary breast cancer. Cancer Discovery, 3, 894–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joshi, S., Tolkunov, D., Aviv, H., Hakimi, A. A., Yao, M., Hsieh, J. J., et al. (2015). The genomic landscape of renal oncocytoma identifies a metabolic barrier to tumorigenesis. Cell Reports, 13, 1895–1908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karsli-Uzunbas, G., Guo, J. Y., Price, S., Teng, X., Laddha, S. V., Khor, S., et al. (2014). Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discovery, 4, 914–927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaur, J., & Debnath, J. (2015). Autophagy at the crossroads of catabolism and anabolism. Nature Reviews Molecular Cell Biology, 16, 461–472.

    Article  CAS  PubMed  Google Scholar 

  • Kaushik, S., Bandyopadhyay, U., Sridhar, S., Kiffin, R., Martinez-Vicente, M., Kon, M., et al. (2011). Chaperone-mediated autophagy at a glance. Journal of Cell Science, 124, 495–499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimmey, J. M., Huynh, J. P., Weiss, L. A., Park, S., Kambal, A., Debnath, J., et al. (2015). Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature, 528, 565–569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kroemer, G. (2015). Autophagy: A druggable process that is deregulated in aging and human disease. Journal of Clinical Investigation, 125, 1–4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Laddha, S. V., Ganesan, S., Chan, C. S., & White, E. (2014). Mutational landscape of the essential autophagy gene BECN1 in human cancers. Molecular Cancer Research, 12, 485–490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, I. H., Kawai, Y., Fergusson, M. M., Rovira, I. I., Bishop, A. J. R., Motoyama, N., et al. (2012). Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science, 336, 225–228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy, J. M. M., Thompson, J. C., Griesinger, A. M., Amani, V., Donson, A. M., Birks, D. K., et al. (2014). Autophagy inhibition improves chemosensitivity in BRAFV600E brain tumors. Cancer Discovery, 4, 773–780.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy, J. M., & Thorburn, A. (2011). Targeting autophagy during cancer therapy to improve clinical outcomes. Pharmacology and Therapeutics, 131, 130–141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy, J. M., & Thorburn, A. (2012). Modulation of pediatric brain tumor autophagy and chemosensitivity. Journal of Neuro-Oncology, 106, 281–290.

    Article  CAS  PubMed  Google Scholar 

  • Li, Y., Hahn, T., Garrison, K., Cui, Z. H., Thorburn, A., Thorburn, J., et al. (2012). The vitamin E analogue alpha-TEA stimulates tumor autophagy and enhances antigen cross-presentation. Cancer Research, 72, 3535–3545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang, X., de Vera, M. E., Buchser, W. J., Romo De Vivar Chavez, A., Loughran, P., Beer Stolz, D., et al. (2012). Inhibiting systemic autophagy during interleukin 2 immunotherapy promotes long-term tumor regression. Cancer Research, 72, 2791–2801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B. H., et al. (2006). Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nature Cell Biology, 8, 688–698.

    Article  CAS  PubMed  Google Scholar 

  • Lock, R., Kenific, C. M., Leidal, A. M., Salas, E., & Debnath, J. (2014). Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discovery, 4, 466–479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lock, R., Roy, S., Kenific, C. M., Su, J. S., Salas, E., Ronen, S. M., et al. (2011). Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Molecular Biology of the Cell, 22, 165–178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma, X.-H., Piao, S.-F., Dey, S., McAfee, Q., Karakousis, G., Villanueva, J., et al. (2014). Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. Journal of Clinical Investigation, 124, 1406–1417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maejima, I., Takahashi, A., Omori, H., Kimura, T., Takabatake, Y., Saitoh, T., et al. (2013). Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. The EMBO Journal, 32, 2336–2347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mancias, J. D., & Kimmelman, A. C. (2011). Targeting autophagy addiction in cancer. Oncotarget, 2, 1302–1306.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mancias, J. D., Wang, X., Gygi, S. P., Harper, J. W., & Kimmelman, A. C. (2014). Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature, 509, 105–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marino, G., Salvador-Montoliu, N., Fueyo, A., Knecht, E., Mizushima, N., & Lopez-Otin, C. (2007). Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. Journal of Biological Chemistry, 282, 18573–18583.

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Lopez, N., Athonvarangkul, D., Mishall, P., Sahu, S., & Singh, R. (2013). Autophagy proteins regulate ERK phosphorylation. Nature Communications, 4, 2799.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maskey, D., Yousefi, S., Schmid, I., Zlobec, I., Perren, A., Friis, R., et al. (2013). ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy. Nature Communications, 4, 2130.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathew, R., Khor, S., Hackett, S. R., Rabinowitz, J. D., Perlman, D. H., & White, E. (2014). Functional role of autophagy-mediated proteome remodeling in cell survival signaling and innate immunity. Molecular Cell, 55, 916–930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maycotte, P., Aryal, S., Cummings, C. T., Thorburn, J., Morgan, M. J., & Thorburn, A. (2012). Chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy. Autophagy, 8, 200–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maycotte, P., Gearheart, C. M., Barnard, R., Aryal, S., Mulcahy Levy, J. M., Fosmire, S. P., et al. (2014). STAT3-mediated autophagy dependence identifies subtypes of breast cancer where autophagy inhibition can be efficacious. Cancer Research, 74, 2579–2590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maycotte, P., Jones, K. L., Goodall, M. L., Thorburn, J., & Thorburn, A. (2015). Autophagy supports breast cancer stem cell maintenance by regulating IL6 secretion. Molecular Cancer Research, 13(4), 651–658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maycotte, P., & Thorburn, A. (2011). Autophagy and cancer therapy. Cancer Biology and Therapy, 11, 127–137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mcafee, Q., Zhang, Z., Samanta, A., Levi, S. M., Ma, X.-H., Piao, S., et al. (2012). Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proceedings of the National Academy of Science of the United States of America, 109(21), 8253–8258.

    Google Scholar 

  • Michaud, M., Martins, I., Sukkurwala, A. Q., Adjemian, S., Ma, Y., Pellegatti, P., et al. (2011). Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science, 334, 1573–1577.

    Article  CAS  PubMed  Google Scholar 

  • Mizushima, N., Yoshimori, T., & Ohsumi, Y. (2011). The role of Atg proteins in autophagosome formation. Annual Review of Cell and Developmental Biology, 27, 107–132.

    Article  CAS  PubMed  Google Scholar 

  • Mochida, K., Oikawa, Y., Kimura, Y., Kirisako, H., Hirano, H., Ohsumi, Y., et al. (2015). Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus. Nature, 522, 359–362.

    Article  CAS  PubMed  Google Scholar 

  • Morgan, M. J., Gamez, G., Menke, C., Hernandez, A., Thorburn, J., Gidan, F., et al. (2014). Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent. Autophagy, 10, 1814–1826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., et al. (2015). Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature, 524, 361–365.

    Article  CAS  PubMed  Google Scholar 

  • Pérez, E., Das, G., Bergmann, A., & Baehrecke, E. H. (2015). Autophagy regulates tissue overgrowth in a context-dependent manner. Oncogene, 34, 3369–3376.

    Article  PubMed  Google Scholar 

  • Petherick, K. J., Conway, O. J. L., Mpamhanga, C., Osborne, S. A., Kamal, A., Saxty, B., et al. (2015). Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. The Journal of Biological Chemistry, 290, 11376–11383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., et al. (2003). Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. Journal of Clinical Investigation, 112, 1809–1820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Radoshevich, L., Murrow, L., Chen, N., Fernandez, E., Roy, S., Fung, C., et al. (2010). ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell, 142, 590–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Randow, F., & Youle, R. J. (2014). Self and nonself: How autophagy targets mitochondria and bacteria. Cell Host & Microbe, 15, 403–411.

    Article  CAS  Google Scholar 

  • Rangwala, R., Chang, Y. C., Hu, J., Algazy, K., Evans, T., Fecher, L., et al. (2014a). Combined MTOR and autophagy inhibition: Phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy, 10, 1391–1402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rangwala, R., Leone, R., Chang, Y. C., Fecher, L., Schuchter, L., Kramer, A., et al. (2014b). Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy, 10, 1369–1379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao, S., Tortola, L., Perlot, T., Wirnsberger, G., Novatchkova, M., Nitsch, R., et al. (2014). A dual role for autophagy in a murine model of lung cancer. Nature Communications, 5, 3056.

    Article  PubMed  Google Scholar 

  • Rebecca, V. W., & Amaravadi, R. K. (2015). Emerging strategies to effectively target autophagy in cancer. Oncogene, 35(11), 1–11.

    PubMed  PubMed Central  Google Scholar 

  • Ronan, B., Flamand, O., Vescovi, L., Dureuil, C., Durand, L., Fassy, F., et al. (2014). A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nature Chemical Biology, 10, 1013–1019.

    Article  CAS  PubMed  Google Scholar 

  • Rosenfeld, M. R., Ye, X., Supko, J. G., Desideri, S., Grossman, S. A., Brem, S., et al. (2014). A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy, 10, 1359–1368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenfeldt, M. T., O’Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., et al. (2013). p53 status determines the role of autophagy in pancreatic tumour development. Nature, 504, 296–300.

    Article  CAS  PubMed  Google Scholar 

  • Rubinstein, A. D., Eisenstein, M., Ber, Y., Bialik, S., & Kimchi, A. (2011). The autophagy protein Atg12 associates with antiapoptotic Bcl-2 family members to promote mitochondrial apoptosis. Molecular Cell, 44, 698–709.

    Article  CAS  PubMed  Google Scholar 

  • Rubinsztein, D. C., Codogno, P., & Levine, B. (2012). Autophagy modulation as a potential therapeutic target for diverse diseases. Nature Reviews Drug Discovery, 11, 709–730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahu, R., Kaushik, S., Clement, C. C., Cannizzo, E. S., Scharf, B., Follenzi, A., et al. (2011). Microautophagy of cytosolic proteins by late endosomes. Developmental Cell, 20, 131–139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen, S., Kepp, O., Michaud, M., Martins, I., Minoux, H., Métivier, D., et al. (2011). Association and dissociation of autophagy, apoptosis and necrosis by systematic chemical study. Oncogene, 30(45), 4544–4556.

    Article  CAS  PubMed  Google Scholar 

  • Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., et al. (2004). Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nature Cell Biology, 6, 1221–1228.

    Article  CAS  PubMed  Google Scholar 

  • Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., et al. (2009). Autophagy regulates lipid metabolism. Nature, 458, 1131–1135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strohecker, A. M., Guo, J. Y., Karsli-Uzunbas, G., Price, S. M., Chen, G. J., Mathew, R., et al. (2013). Autophagy sustains mitochondrial glutamine metabolism and growth of BRAFV600E-driven lung tumors. Cancer Discovery, 3, 1272–1285.

    Article  CAS  PubMed  Google Scholar 

  • Subramani, S., & Malhotra, V. (2013). Non-autophagic roles of autophagy-related proteins. EMBO Reports, 14, 143–151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi, Y., Coppola, D., Matsushita, N., Cualing, H. D., Sun, M., Sato, Y., et al. (2007). Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nature Cell Biology, 9, 1142–1151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takamura, A., Komatsu, M., Hara, T., Sakamoto, A., Kishi, C., Waguri, S., et al. (2011). Autophagy-deficient mice develop multiple liver tumors. Genes and Development, 25, 795–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang, H., Sebti, S., Titone, R., Zhou, Y., Isidoro, C., Ross, T. S., et al. (2015). Decreased BECN1 mRNA expression in human breast cancer is associated with estrogen receptor-negative subtypes and poor prognosis. EBioMedicine, 2, 255–263.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thorburn, A. (2008). Studying autophagy’s relationship to cell death. Autophagy, 4, 391–394.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thorburn, A. (2011). I think autophagy controls the death of my cells: What do I do to get my paper published? Autophagy, 7, 455–456.

    Article  PubMed  Google Scholar 

  • Thorburn, A. (2014). Autophagy and its effects: Making sense of double-edged swords. PLoS Biology, 12, e1001967.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thorburn, J., Horita, H., Redzic, J., Hansen, K., Frankel, A. E., & Thorburn, A. (2009). Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. Cell Death and Differentiation, 16, 175–183.

    Article  CAS  PubMed  Google Scholar 

  • Thorburn, A., & Morgan, M. J. (2015). Targeting autophagy in BRAF-mutant tumors. Cancer Discovery, 5, 353–354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorburn, A., Thamm, D. H., & Gustafson, D. L. (2014). Autophagy and cancer therapy. Molecular Pharmacology, 85, 830–838.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thoresen, S. B., Pedersen, N. M., Liestøl, K., & Stenmark, H. (2010). A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Experimental Cell Research, 316, 3368–3378.

    Article  CAS  PubMed  Google Scholar 

  • Veldhoen, R. A., Banman, S. L., Hemmerling, D. R., Odsen, R., Simmen, T., Simmonds, A. J., et al. (2013). The chemotherapeutic agent paclitaxel inhibits autophagy through two distinct mechanisms that regulate apoptosis. Oncogene, 32, 736–746.

    Article  CAS  PubMed  Google Scholar 

  • Vogl, D. T., Stadtmauer, E. A., Tan, K.-S., Heitjan, D. F., Davis, L. E., Pontiggia, L., et al. (2014). Combined autophagy and proteasome inhibition: A phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy, 10, 1380–1390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei, H., Wang, C., Croce, C. M., & Guan, J.-L. (2014). p62/SQSTM1 synergizes with autophagy for tumor growth in vivo. Genes and Development, 28, 1204–1216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei, H., Wei, S., Gan, B., Peng, X., Zou, W., & Guan, J.-L. (2011). Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes and Development, 25, 1510–1527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei, Y., Zou, Z., Becker, N., Anderson, M., Sumpter, R., Xiao, G., et al. (2013). EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell, 154, 1269–1284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White, E. (2012). Deconvoluting the context-dependent role for autophagy in cancer. Nature Reviews Cancer, 12, 401–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolpin, B. M., Rubinson, D. A., Wang, X., Chan, J. A., Cleary, J. M., Enzinger, P. C., et al. (2014). Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. The Oncologist, 19, 637–638.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xie, X., Koh, J. Y., Price, S., White, E., & Mehnert, J. M. (2015). Atg7 overcomes senescence and promotes growth of BrafV600E-driven melanoma. Cancer Discovery, 5, 410–423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie, X., White, E. P., & Mehnert, J. M. (2013). Coordinate autophagy and mTOR pathway inhibition enhances cell death in melanoma. PLoS One, 8, e55096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, A., Rajeshkumar, N. V., Wang, X., Yabuuchi, S., Alexander, B. M., Chu, G. C., et al. (2014). Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations. Cancer Discovery, 4, 905–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., et al. (2011). Pancreatic cancers require autophagy for tumor growth. Genes and Development, 25, 717–729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003). Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proceedings of the National Academy of Sciences of the United States of America, 100, 15077–15082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, Z., Oh, S., Li, D., Ni, D., Pirooz, S. D., Lee, J.-H., et al. (2012). A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Developmental Cell, 22(5), 1001–1016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA

    Jenny Mae Samson & Andrew Thorburn

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  1. Jenny Mae Samson
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  2. Andrew Thorburn
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Correspondence to Andrew Thorburn .

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  1. Department of Pharmacology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA

    Jin-Ming Yang

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Samson, J.M., Thorburn, A. (2016). Autophagy as a Therapeutic Target in Cancer. In: Yang, JM. (eds) Targeting Autophagy in Cancer Therapy. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-319-42740-9_1

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  • DOI: https://doi.org/10.1007/978-3-319-42740-9_1

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