Skip to main content
Top
Published in: Current Treatment Options in Oncology 2/2023

Open Access 21-01-2023 | Chloroquin | Skin Cancer (T Ito, Section Editor)

Autophagy Paradox: Strategizing Treatment Modality in Melanoma

Authors: Christian Pangilinan, PhD, Xiaowei Xu, MD, PhD, Meenhard Herlyn, DVM, DSc, Chengyu Liang, MD, PhD

Published in: Current Treatment Options in Oncology | Issue 2/2023

Login to get access

Opinion statement

The primordial autophagy process, originally identified as a starvation response in baker’s yeast, has since been shown to have a wide spectrum of functions other than survival. In many cases, it is accepted that autophagy operates as a key tumor suppressor mechanism that protects cells from adverse environmental cues by enforcing homeostasis and maintaining the functional and structural integrity of organelles. Paradoxically, heightened states of autophagy are also seen in some cancers, leading to the prevailing view that the pro-survival aspect of autophagy might be hijacked by some tumors to promote their fitness and pathogenesis. Notably, recent studies have revealed a broad range of cell-autonomous autophagy in reshaping tumor microenvironment and maintaining lineage integrity and immune homeostasis, calling for a renewed understanding of autophagy beyond its classical roles in cell survival. Here, we evaluate the increasing body of literature that argues the “double-edged” consequences of autophagy manipulation in cancer therapy, with a particular focus on highly plastic and mutagenic melanoma. We also discuss the caveats that must be considered when evaluating whether autophagy blockade is the effector mechanism of some anti-cancer therapy particularly associated with lysosomotropic agents. If autophagy proteins are to be properly exploited as targets for anticancer drugs, their diverse and complex roles should also be considered.
Literature
1.
go back to reference Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. Ca-Cancer J Clin. 2022;72(1):7–33.CrossRef Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. Ca-Cancer J Clin. 2022;72(1):7–33.CrossRef
2.
go back to reference Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.CrossRef Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.CrossRef
3.
go back to reference Luke JJ, Flaherty KT, Ribas A, Long GV. Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol. 2017;14(8):463–82.CrossRef Luke JJ, Flaherty KT, Ribas A, Long GV. Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol. 2017;14(8):463–82.CrossRef
4.
go back to reference Wagle N, Van Allen EM, Treacy DJ, Frederick DT, Cooper ZA, Taylor-Weiner A, et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 2014;4(1):61–8.CrossRef Wagle N, Van Allen EM, Treacy DJ, Frederick DT, Cooper ZA, Taylor-Weiner A, et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 2014;4(1):61–8.CrossRef
5.
go back to reference Tran KB, Buchanan CM, Shepherd PR. Evolution of molecular targets in melanoma treatment. Curr Pharm Des. 2020;26(4):396–414.CrossRef Tran KB, Buchanan CM, Shepherd PR. Evolution of molecular targets in melanoma treatment. Curr Pharm Des. 2020;26(4):396–414.CrossRef
6.
go back to reference Rambow F, Marine JC, Goding CR. Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities. Gene Dev. 2019;33(19-20):1295–318.CrossRef Rambow F, Marine JC, Goding CR. Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities. Gene Dev. 2019;33(19-20):1295–318.CrossRef
7.
go back to reference Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333(1-2):169–74.CrossRef Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333(1-2):169–74.CrossRef
8.
go back to reference Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368(7):651–62.CrossRef Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368(7):651–62.CrossRef
9.
go back to reference Klionsky DJ. The molecular machinery of autophagy: unanswered questions. J Cell Sci. 2005;118(Pt 1):7–18.CrossRef Klionsky DJ. The molecular machinery of autophagy: unanswered questions. J Cell Sci. 2005;118(Pt 1):7–18.CrossRef
10.
go back to reference Cuervo AM, Wong E. Chaperone-mediated autophagy: roles in disease and aging. Cell Res. 2014;24(1):92–104.CrossRef Cuervo AM, Wong E. Chaperone-mediated autophagy: roles in disease and aging. Cell Res. 2014;24(1):92–104.CrossRef
11.
go back to reference Schuck S. Microautophagy - distinct molecular mechanisms handle cargoes of many sizes. J Cell Sci. 2020;133(17). Schuck S. Microautophagy - distinct molecular mechanisms handle cargoes of many sizes. J Cell Sci. 2020;133(17).
12.
go back to reference Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157(1):65–75.CrossRef Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157(1):65–75.CrossRef
13.
go back to reference Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–31.CrossRef Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–31.CrossRef
14.
go back to reference Trefts E, Shaw RJ. AMPK: restoring metabolic homeostasis over space and time. Mol Cell. 2021;81(18):3677–90.CrossRef Trefts E, Shaw RJ. AMPK: restoring metabolic homeostasis over space and time. Mol Cell. 2021;81(18):3677–90.CrossRef
15.
go back to reference Roczniak-Ferguson A, Petit CS, Froehlich F, Qian S, Ky J, Angarola B, et al. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012;5(228):ra42. Roczniak-Ferguson A, Petit CS, Froehlich F, Qian S, Ky J, Angarola B, et al. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012;5(228):ra42.
16.
go back to reference Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27–42.CrossRef Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27–42.CrossRef
17.
go back to reference Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol. 2008;9(12):1004–10.CrossRef Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol. 2008;9(12):1004–10.CrossRef
18.
go back to reference Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest. 2005;115(10):2679–88.CrossRef Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest. 2005;115(10):2679–88.CrossRef
19.
go back to reference Perrotta C, Cattaneo MG, Molteni R, De Palma C. Autophagy in the regulation of tissue differentiation and homeostasis. Front Cell Dev Biol. 2020;8:602901.CrossRef Perrotta C, Cattaneo MG, Molteni R, De Palma C. Autophagy in the regulation of tissue differentiation and homeostasis. Front Cell Dev Biol. 2020;8:602901.CrossRef
20.
go back to reference Galluzzi L, Green DR. Autophagy-independent functions of the autophagy machinery. Cell. 2019;177(7):1682–99.CrossRef Galluzzi L, Green DR. Autophagy-independent functions of the autophagy machinery. Cell. 2019;177(7):1682–99.CrossRef
21.
go back to reference Cao Y, Klionsky DJ. Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res. 2007;17(10):839–49.CrossRef Cao Y, Klionsky DJ. Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res. 2007;17(10):839–49.CrossRef
22.
go back to reference Yang Y, He S, Wang Q, Li F, Kwak MJ, Chen S, et al. Autophagic UVRAG promotes UV-induced photolesion repair by activation of the CRL4(DDB2) E3 ligase. Mol Cell. 2016;62(4):507–19.CrossRef Yang Y, He S, Wang Q, Li F, Kwak MJ, Chen S, et al. Autophagic UVRAG promotes UV-induced photolesion repair by activation of the CRL4(DDB2) E3 ligase. Mol Cell. 2016;62(4):507–19.CrossRef
23.
go back to reference Zhao Z, Oh S, Li D, Ni D, Pirooz SD, Lee JH, et al. A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Dev Cell. 2012;22(5):1001–16.CrossRef Zhao Z, Oh S, Li D, Ni D, Pirooz SD, Lee JH, et al. A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Dev Cell. 2012;22(5):1001–16.CrossRef
24.
go back to reference Lee IH, Kawai Y, Fergusson MM, Rovira II, Bishop AJ, Motoyama N, et al. Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science. 2012;336(6078):225–8.CrossRef Lee IH, Kawai Y, Fergusson MM, Rovira II, Bishop AJ, Motoyama N, et al. Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science. 2012;336(6078):225–8.CrossRef
25.
go back to reference Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447(7148):1121–5.CrossRef Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447(7148):1121–5.CrossRef
26.
go back to reference Maiani E, Milletti G, Nazio F, Holdgaard SG, Bartkova J, Rizza S, et al. AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature. 2021;592(7856):799–803.CrossRef Maiani E, Milletti G, Nazio F, Holdgaard SG, Bartkova J, Rizza S, et al. AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature. 2021;592(7856):799–803.CrossRef
27.
go back to reference • Chaikovsky AC, Li C, Jeng EE, Loebell S, Lee MC, Murray CW, et al. The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D. Nature. 2021;592(7856):794–8 Uncovering a new molecular mechansim of autophagy-related AMBRA1 protein in governing cell growth control through D-type cyclin.CrossRef • Chaikovsky AC, Li C, Jeng EE, Loebell S, Lee MC, Murray CW, et al. The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D. Nature. 2021;592(7856):794–8 Uncovering a new molecular mechansim of autophagy-related AMBRA1 protein in governing cell growth control through D-type cyclin.CrossRef
28.
go back to reference Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015;34(7):856–80.CrossRef Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015;34(7):856–80.CrossRef
29.
go back to reference Zhong Z, Sanchez-Lopez E, Karin M. Autophagy, inflammation, and immunity: a Troika governing cancer and its treatment. Cell. 2016;166(2):288–98.CrossRef Zhong Z, Sanchez-Lopez E, Karin M. Autophagy, inflammation, and immunity: a Troika governing cancer and its treatment. Cell. 2016;166(2):288–98.CrossRef
30.
go back to reference White E. The role for autophagy in cancer. J Clin Invest. 2015;125(1):42–6.CrossRef White E. The role for autophagy in cancer. J Clin Invest. 2015;125(1):42–6.CrossRef
31.
go back to reference Liu H, He Z, von Rutte T, Yousefi S, Hunger RE, Simon HU. Down-regulation of autophagy-related protein 5 (ATG5) contributes to the pathogenesis of early-stage cutaneous melanoma. Sci Transl Med. 2013;5(202):202ra123.CrossRef Liu H, He Z, von Rutte T, Yousefi S, Hunger RE, Simon HU. Down-regulation of autophagy-related protein 5 (ATG5) contributes to the pathogenesis of early-stage cutaneous melanoma. Sci Transl Med. 2013;5(202):202ra123.CrossRef
32.
go back to reference Frangez Z, Gerard D, He Z, Gavriil M, Fernandez-Marrero Y, Seyed Jafari SM, et al. ATG5 and ATG7 expression levels are reduced in cutaneous melanoma and regulated by NRF1. Front Oncol. 2021;11:721624.CrossRef Frangez Z, Gerard D, He Z, Gavriil M, Fernandez-Marrero Y, Seyed Jafari SM, et al. ATG5 and ATG7 expression levels are reduced in cutaneous melanoma and regulated by NRF1. Front Oncol. 2021;11:721624.CrossRef
33.
go back to reference Garcia-Fernandez M, Karras P, Checinska A, Canon E, Calvo GT, Gomez-Lopez G, et al. Metastatic risk and resistance to BRAF inhibitors in melanoma defined by selective allelic loss of ATG5. Autophagy. 2016;12(10):1776–90.CrossRef Garcia-Fernandez M, Karras P, Checinska A, Canon E, Calvo GT, Gomez-Lopez G, et al. Metastatic risk and resistance to BRAF inhibitors in melanoma defined by selective allelic loss of ATG5. Autophagy. 2016;12(10):1776–90.CrossRef
34.
go back to reference Rosenfeldt MT, O'Prey J, Lindsay CR, Nixon C, Roth S, Sansom OJ, et al. Loss of autophagy affects melanoma development in a manner dependent on PTEN status. Cell Death Differ. 2021;28(4):1437–9.CrossRef Rosenfeldt MT, O'Prey J, Lindsay CR, Nixon C, Roth S, Sansom OJ, et al. Loss of autophagy affects melanoma development in a manner dependent on PTEN status. Cell Death Differ. 2021;28(4):1437–9.CrossRef
35.
go back to reference Xie X, Koh JY, Price S, White E, Mehnert JM. Atg7 overcomes senescence and promotes growth of BrafV600E-driven melanoma. Cancer Discov. 2015;5(4):410–23.CrossRef Xie X, Koh JY, Price S, White E, Mehnert JM. Atg7 overcomes senescence and promotes growth of BrafV600E-driven melanoma. Cancer Discov. 2015;5(4):410–23.CrossRef
36.
go back to reference Rosenfeldt MT, O'Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature. 2013;504(7479):296–300.CrossRef Rosenfeldt MT, O'Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature. 2013;504(7479):296–300.CrossRef
37.
go back to reference Ma XH, Piao SF, Dey S, McAfee Q, Karakousis G, Villanueva J, et al. Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest. 2014;124(3):1406–17.CrossRef Ma XH, Piao SF, Dey S, McAfee Q, Karakousis G, Villanueva J, et al. Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest. 2014;124(3):1406–17.CrossRef
38.
go back to reference Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363(9):809–19.CrossRef Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363(9):809–19.CrossRef
39.
go back to reference Corazzari M, Rapino F, Ciccosanti F, Giglio P, Antonioli M, Conti B, et al. Oncogenic BRAF induces chronic ER stress condition resulting in increased basal autophagy and apoptotic resistance of cutaneous melanoma. Cell Death Differ. 2015;22(6):946–58.CrossRef Corazzari M, Rapino F, Ciccosanti F, Giglio P, Antonioli M, Conti B, et al. Oncogenic BRAF induces chronic ER stress condition resulting in increased basal autophagy and apoptotic resistance of cutaneous melanoma. Cell Death Differ. 2015;22(6):946–58.CrossRef
40.
go back to reference Mandula JK, Chang S, Mohamed E, Jimenez R, Sierra-Mondragon RA, Chang DC, et al. Ablation of the endoplasmic reticulum stress kinase PERK induces paraptosis and type I interferon to promote anti-tumor T cell responses. Cancer Cell. 2022;40(10):1145–60 e9.CrossRef Mandula JK, Chang S, Mohamed E, Jimenez R, Sierra-Mondragon RA, Chang DC, et al. Ablation of the endoplasmic reticulum stress kinase PERK induces paraptosis and type I interferon to promote anti-tumor T cell responses. Cancer Cell. 2022;40(10):1145–60 e9.CrossRef
41.••
go back to reference Li S, Song Y, Quach C, Guo H, Jang GB, Maazi H, et al. Transcriptional regulation of autophagy-lysosomal function in BRAF-driven melanoma progression and chemoresistance. Nat Commun. 2019;10(1):1693 A study demonstrating the molecular mechanisms underlying BRAFi-associated autophagy-lysosome activation and its implication in melanoma progression, metastasis, and drug resistance. Li S, Song Y, Quach C, Guo H, Jang GB, Maazi H, et al. Transcriptional regulation of autophagy-lysosomal function in BRAF-driven melanoma progression and chemoresistance. Nat Commun. 2019;10(1):1693 A study demonstrating the molecular mechanisms underlying BRAFi-associated autophagy-lysosome activation and its implication in melanoma progression, metastasis, and drug resistance.
42.
go back to reference Yeom H, Hwang SH, Han BI, Lee M. Differential sensitivity of wild-type and BRAF-mutated cells to combined BRAF and autophagy inhibition. Biomol Ther (Seoul). 2021;29(4):434–44.CrossRef Yeom H, Hwang SH, Han BI, Lee M. Differential sensitivity of wild-type and BRAF-mutated cells to combined BRAF and autophagy inhibition. Biomol Ther (Seoul). 2021;29(4):434–44.CrossRef
43.
go back to reference Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G, et al. EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell. 2013;154(6):1269–84.CrossRef Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G, et al. EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell. 2013;154(6):1269–84.CrossRef
44.•
go back to reference Marsh T, Kenific CM, Suresh D, Gonzalez H, Shamir ER, Mei W, et al. Autophagic degradation of NBR1 restricts metastatic outgrowth during mammary tumor progression. Dev Cell. 2020;52(5):591–604 e6 Preclinical evidence showing how autophagy ablation could exacerbate tumor metastasis. Marsh T, Kenific CM, Suresh D, Gonzalez H, Shamir ER, Mei W, et al. Autophagic degradation of NBR1 restricts metastatic outgrowth during mammary tumor progression. Dev Cell. 2020;52(5):591–604 e6 Preclinical evidence showing how autophagy ablation could exacerbate tumor metastasis.
45.
go back to reference Ma Y, Galluzzi L, Zitvogel L, Kroemer G. Autophagy and cellular immune responses. Immunity. 2013;39(2):211–27.CrossRef Ma Y, Galluzzi L, Zitvogel L, Kroemer G. Autophagy and cellular immune responses. Immunity. 2013;39(2):211–27.CrossRef
46.
go back to reference Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, et al. Fasting-mimicking diet reduces HO-1 to promote T cell-mediated tumor cytotoxicity. Cancer Cell. 2016;30(1):136–46.CrossRef Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, et al. Fasting-mimicking diet reduces HO-1 to promote T cell-mediated tumor cytotoxicity. Cancer Cell. 2016;30(1):136–46.CrossRef
47.
go back to reference Pietrocola F, Pol J, Kroemer G. Fasting improves anticancer immunosurveillance via autophagy induction in malignant cells. Cell Cycle. 2016;15(24):3327–8.CrossRef Pietrocola F, Pol J, Kroemer G. Fasting improves anticancer immunosurveillance via autophagy induction in malignant cells. Cell Cycle. 2016;15(24):3327–8.CrossRef
48.
go back to reference Castoldi F, Vacchelli E, Zitvogel L, Maiuri MC, Pietrocola F, Kroemer G. Systemic autophagy in the therapeutic response to anthracycline-based chemotherapy. Oncoimmunology. 2019;8(1):e1498285.CrossRef Castoldi F, Vacchelli E, Zitvogel L, Maiuri MC, Pietrocola F, Kroemer G. Systemic autophagy in the therapeutic response to anthracycline-based chemotherapy. Oncoimmunology. 2019;8(1):e1498285.CrossRef
49.
go back to reference •• Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, et al. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 2020;581(7806):100–5 A seminar work revealing how pancreatic cancer-associated autophagy promotes tumor immune evasion through downregulation of MHC-I.CrossRef •• Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, et al. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 2020;581(7806):100–5 A seminar work revealing how pancreatic cancer-associated autophagy promotes tumor immune evasion through downregulation of MHC-I.CrossRef
50.
go back to reference Yamazaki T, Kirchmair A, Sato A, Buque A, Rybstein M, Petroni G, et al. Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy. Nat Immunol. 2020;21(10):1160–71.CrossRef Yamazaki T, Kirchmair A, Sato A, Buque A, Rybstein M, Petroni G, et al. Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy. Nat Immunol. 2020;21(10):1160–71.CrossRef
51.
go back to reference Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–14.CrossRef Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–14.CrossRef
52.
go back to reference Shukla SA, Bachireddy P, Schilling B, Galonska C, Zhan Q, Bango C, et al. Cancer-germline antigen expression discriminates clinical outcome to CTLA-4 blockade. Cell. 2018;173(3):624–33 e8.CrossRef Shukla SA, Bachireddy P, Schilling B, Galonska C, Zhan Q, Bango C, et al. Cancer-germline antigen expression discriminates clinical outcome to CTLA-4 blockade. Cell. 2018;173(3):624–33 e8.CrossRef
53.
go back to reference Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6(2):202–16.CrossRef Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6(2):202–16.CrossRef
54.
go back to reference Michaud M, Xie X, Bravo-San Pedro JM, Zitvogel L, White E, Kroemer G. An autophagy-dependent anticancer immune response determines the efficacy of melanoma chemotherapy. Oncoimmunology. 2014;3(7):e944047.CrossRef Michaud M, Xie X, Bravo-San Pedro JM, Zitvogel L, White E, Kroemer G. An autophagy-dependent anticancer immune response determines the efficacy of melanoma chemotherapy. Oncoimmunology. 2014;3(7):e944047.CrossRef
55.
go back to reference Florencio KGD, Edson EA, Fernandes K, Luiz JPM, Pinto F, Pessoa ODL, et al. Chromomycin A(5) induces bona fide immunogenic cell death in melanoma. Front Immunol. 2022;13:941757.CrossRef Florencio KGD, Edson EA, Fernandes K, Luiz JPM, Pinto F, Pessoa ODL, et al. Chromomycin A(5) induces bona fide immunogenic cell death in melanoma. Front Immunol. 2022;13:941757.CrossRef
56.
go back to reference Zhou H, Tu C, Yang P, Li J, Kepp O, Li H, et al. Carbon ion radiotherapy triggers immunogenic cell death and sensitizes melanoma to anti-PD-1 therapy in mice. Oncoimmunology. 2022;11(1):2057892.CrossRef Zhou H, Tu C, Yang P, Li J, Kepp O, Li H, et al. Carbon ion radiotherapy triggers immunogenic cell death and sensitizes melanoma to anti-PD-1 therapy in mice. Oncoimmunology. 2022;11(1):2057892.CrossRef
57.
go back to reference Ciardiello D, Elez E, Tabernero J, Seoane J. Clinical development of therapies targeting TGFbeta: current knowledge and future perspectives. Ann Oncol. 2020;31(10):1336–49.CrossRef Ciardiello D, Elez E, Tabernero J, Seoane J. Clinical development of therapies targeting TGFbeta: current knowledge and future perspectives. Ann Oncol. 2020;31(10):1336–49.CrossRef
58.
go back to reference Horn LA, Chariou PL, Gameiro SR, Qin H, Iida M, Fousek K, et al. Remodeling the tumor microenvironment via blockade of LAIR-1 and TGF-beta signaling enables PD-L1-mediated tumor eradication. J Clin Invest. 2022;132(8). Horn LA, Chariou PL, Gameiro SR, Qin H, Iida M, Fousek K, et al. Remodeling the tumor microenvironment via blockade of LAIR-1 and TGF-beta signaling enables PD-L1-mediated tumor eradication. J Clin Invest. 2022;132(8).
59.
go back to reference Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, Iglesias M, et al. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018;554(7693):538–43.CrossRef Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, Iglesias M, et al. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018;554(7693):538–43.CrossRef
60.
go back to reference Mgrditchian T, Arakelian T, Paggetti J, Noman MZ, Viry E, Moussay E, et al. Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner. Proc Natl Acad Sci U S A. 2017;114(44):E9271–E9.CrossRef Mgrditchian T, Arakelian T, Paggetti J, Noman MZ, Viry E, Moussay E, et al. Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner. Proc Natl Acad Sci U S A. 2017;114(44):E9271–E9.CrossRef
61.
go back to reference Wang S, Xia P, Huang G, Zhu P, Liu J, Ye B, et al. FoxO1-mediated autophagy is required for NK cell development and innate immunity. Nat Commun. 2016;7:11023.CrossRef Wang S, Xia P, Huang G, Zhu P, Liu J, Ye B, et al. FoxO1-mediated autophagy is required for NK cell development and innate immunity. Nat Commun. 2016;7:11023.CrossRef
62.
go back to reference Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res. 2011;17(4):654–66.CrossRef Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res. 2011;17(4):654–66.CrossRef
63.
go back to reference Gallagher LE, Radhi OA, Abdullah MO, McCluskey AG, Boyd M, Chan EYW. Lysosomotropism depends on glucose: a chloroquine resistance mechanism. Cell Death Dis. 2017;8(8):e3014.CrossRef Gallagher LE, Radhi OA, Abdullah MO, McCluskey AG, Boyd M, Chan EYW. Lysosomotropism depends on glucose: a chloroquine resistance mechanism. Cell Death Dis. 2017;8(8):e3014.CrossRef
64.
go back to reference Kroemer G, Jaattela M. Lysosomes and autophagy in cell death control. Nat Rev Cancer. 2005;5(11):886–97.CrossRef Kroemer G, Jaattela M. Lysosomes and autophagy in cell death control. Nat Rev Cancer. 2005;5(11):886–97.CrossRef
65.
go back to reference Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst. 2004;96(22):1702–13.CrossRef Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst. 2004;96(22):1702–13.CrossRef
66.
go back to reference Sarkar S, Bisoi A, Singh PC. Spectroscopic and molecular dynamics aspect of antimalarial drug hydroxychloroquine binding with human telomeric G-quadruplex. J Phys Chem B. 2022;126(28):5241–9.CrossRef Sarkar S, Bisoi A, Singh PC. Spectroscopic and molecular dynamics aspect of antimalarial drug hydroxychloroquine binding with human telomeric G-quadruplex. J Phys Chem B. 2022;126(28):5241–9.CrossRef
67.
go back to reference Rebecca VW, Nicastri MC, Fennelly C, Chude CI, Barber-Rotenberg JS, Ronghe A, et al. PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discov. 2019;9(2):220–9.CrossRef Rebecca VW, Nicastri MC, Fennelly C, Chude CI, Barber-Rotenberg JS, Ronghe A, et al. PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discov. 2019;9(2):220–9.CrossRef
68.
go back to reference Yang S, Qiang L, Sample A, Shah P, He YY. NF-kappaB signaling activation induced by chloroquine requires autophagosome, p62 protein, and c-Jun N-terminal kinase (JNK) signaling and promotes tumor cell resistance. J Biol Chem. 2017;292(8):3379–88.CrossRef Yang S, Qiang L, Sample A, Shah P, He YY. NF-kappaB signaling activation induced by chloroquine requires autophagosome, p62 protein, and c-Jun N-terminal kinase (JNK) signaling and promotes tumor cell resistance. J Biol Chem. 2017;292(8):3379–88.CrossRef
69.
go back to reference Chen D, Xie J, Fiskesund R, Dong W, Liang X, Lv J, et al. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat Commun. 2018;9(1):873.CrossRef Chen D, Xie J, Fiskesund R, Dong W, Liang X, Lv J, et al. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat Commun. 2018;9(1):873.CrossRef
70.
go back to reference Accapezzato D, Visco V, Francavilla V, Molette C, Donato T, Paroli M, et al. Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. J Exp Med. 2005;202(6):817–28.CrossRef Accapezzato D, Visco V, Francavilla V, Molette C, Donato T, Paroli M, et al. Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. J Exp Med. 2005;202(6):817–28.CrossRef
71.
go back to reference Lakhter AJ, Sahu RP, Sun Y, Kaufmann WK, Androphy EJ, Travers JB, et al. Chloroquine promotes apoptosis in melanoma cells by inhibiting BH3 domain-mediated PUMA degradation. J Invest Dermatol. 2013;133(9):2247–54.CrossRef Lakhter AJ, Sahu RP, Sun Y, Kaufmann WK, Androphy EJ, Travers JB, et al. Chloroquine promotes apoptosis in melanoma cells by inhibiting BH3 domain-mediated PUMA degradation. J Invest Dermatol. 2013;133(9):2247–54.CrossRef
72.
go back to reference Eng CH, Wang Z, Tkach D, Toral-Barza L, Ugwonali S, Liu S, et al. Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc Natl Acad Sci U S A. 2016;113(1):182–7.CrossRef Eng CH, Wang Z, Tkach D, Toral-Barza L, Ugwonali S, Liu S, et al. Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc Natl Acad Sci U S A. 2016;113(1):182–7.CrossRef
73.
go back to reference Tian AL, Wu Q, Liu P, Zhao L, Martins I, Kepp O, et al. Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response. Cell Death Dis. 2021;12(1):6.CrossRef Tian AL, Wu Q, Liu P, Zhao L, Martins I, Kepp O, et al. Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response. Cell Death Dis. 2021;12(1):6.CrossRef
74.
go back to reference Zhitomirsky B, Yunaev A, Kreiserman R, Kaplan A, Stark M, Assaraf YG. Lysosomotropic drugs activate TFEB via lysosomal membrane fluidization and consequent inhibition of mTORC1 activity. Cell Death Dis. 2018;9(12):1191.CrossRef Zhitomirsky B, Yunaev A, Kreiserman R, Kaplan A, Stark M, Assaraf YG. Lysosomotropic drugs activate TFEB via lysosomal membrane fluidization and consequent inhibition of mTORC1 activity. Cell Death Dis. 2018;9(12):1191.CrossRef
75.
go back to reference Rubinsztein DC, Codogno P, Levine B. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov. 2012;11(9):709–30.CrossRef Rubinsztein DC, Codogno P, Levine B. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov. 2012;11(9):709–30.CrossRef
76.
go back to reference Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, et al. Autophagy in major human diseases. EMBO J. 2021;40(19):e108863.CrossRef Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, et al. Autophagy in major human diseases. EMBO J. 2021;40(19):e108863.CrossRef
77.
go back to reference Galluzzi L, Bravo-San Pedro JM, Levine B, Green DR, Kroemer G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16(7):487–511.CrossRef Galluzzi L, Bravo-San Pedro JM, Levine B, Green DR, Kroemer G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16(7):487–511.CrossRef
78.
go back to reference Shoji-Kawata S, Sumpter R, Leveno M, Campbell GR, Zou Z, Kinch L, et al. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 2013;494(7436):201–6.CrossRef Shoji-Kawata S, Sumpter R, Leveno M, Campbell GR, Zou Z, Kinch L, et al. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 2013;494(7436):201–6.CrossRef
79.
go back to reference Lee JS, Li Q, Lee JY, Lee SH, Jeong JH, Lee HR, et al. FLIP-mediated autophagy regulation in cell death control. Nat Cell Biol. 2009;11(11):1355–62.CrossRef Lee JS, Li Q, Lee JY, Lee SH, Jeong JH, Lee HR, et al. FLIP-mediated autophagy regulation in cell death control. Nat Cell Biol. 2009;11(11):1355–62.CrossRef
80.
go back to reference Vega-Rubin-de-Celis S, Zou Z, Fernandez AF, Ci B, Kim M, Xiao G, et al. Increased autophagy blocks HER2-mediated breast tumorigenesis. Proc Natl Acad Sci U S A. 2018;115(16):4176–81.CrossRef Vega-Rubin-de-Celis S, Zou Z, Fernandez AF, Ci B, Kim M, Xiao G, et al. Increased autophagy blocks HER2-mediated breast tumorigenesis. Proc Natl Acad Sci U S A. 2018;115(16):4176–81.CrossRef
81.
go back to reference Noman MZ, Parpal S, Van Moer K, Xiao M, Yu Y, Viklund J, et al. Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti-PD-1/PD-L1 immunotherapy. Sci Adv. 2020;6(18):eaax7881.CrossRef Noman MZ, Parpal S, Van Moer K, Xiao M, Yu Y, Viklund J, et al. Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti-PD-1/PD-L1 immunotherapy. Sci Adv. 2020;6(18):eaax7881.CrossRef
82.
go back to reference Bao Y, Ding Z, Zhao P, Li J, Chen P, Zheng J, et al. Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-beta/Smad3 signaling in melanoma cells. Cell Death Dis. 2020;11(4):223.CrossRef Bao Y, Ding Z, Zhao P, Li J, Chen P, Zheng J, et al. Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-beta/Smad3 signaling in melanoma cells. Cell Death Dis. 2020;11(4):223.CrossRef
83.
go back to reference Xia Y, Xu F, Xiong M, Yang H, Lin W, Xie Y, et al. Repurposing of antipsychotic trifluoperazine for treating brain metastasis, lung metastasis and bone metastasis of melanoma by disrupting autophagy flux. Pharmacol Res. 2021;163:105295.CrossRef Xia Y, Xu F, Xiong M, Yang H, Lin W, Xie Y, et al. Repurposing of antipsychotic trifluoperazine for treating brain metastasis, lung metastasis and bone metastasis of melanoma by disrupting autophagy flux. Pharmacol Res. 2021;163:105295.CrossRef
84.
go back to reference Liu Y, Hao Y, Li Y, Zheng Y, Dai J, Zhong F, et al. Salinomycin induces autophagic cell death in salinomycin-sensitive melanoma cells through inhibition of autophagic flux. Sci Rep. 2020;10(1):18515.CrossRef Liu Y, Hao Y, Li Y, Zheng Y, Dai J, Zhong F, et al. Salinomycin induces autophagic cell death in salinomycin-sensitive melanoma cells through inhibition of autophagic flux. Sci Rep. 2020;10(1):18515.CrossRef
85.
go back to reference Dal Yontem F, Kim SH, Ding Z, Grimm E, Ekmekcioglu S, Akcakaya H. Mitochondrial dynamic alterations regulate melanoma cell progression. J Cell Biochem. 2018. Dal Yontem F, Kim SH, Ding Z, Grimm E, Ekmekcioglu S, Akcakaya H. Mitochondrial dynamic alterations regulate melanoma cell progression. J Cell Biochem. 2018.
86.
go back to reference Chen L, Chen Q, Deng G, Kuang S, Lian J, Wang M, et al. AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo. Biochem Biophys Res Commun. 2016;480(4):515–21.CrossRef Chen L, Chen Q, Deng G, Kuang S, Lian J, Wang M, et al. AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo. Biochem Biophys Res Commun. 2016;480(4):515–21.CrossRef
87.
go back to reference Vera Aguilera J, Rao RD, Allred JB, Suman VJ, Windschitl HE, Kaur JS, et al. Phase II study of everolimus in metastatic malignant melanoma (NCCTG-N0377, Alliance). Oncologist. 2018;23(8):887–e94.CrossRef Vera Aguilera J, Rao RD, Allred JB, Suman VJ, Windschitl HE, Kaur JS, et al. Phase II study of everolimus in metastatic malignant melanoma (NCCTG-N0377, Alliance). Oncologist. 2018;23(8):887–e94.CrossRef
88.
go back to reference Gong C, Xia H. Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway. Exp Ther Med. 2020;19(3):1878–86. Gong C, Xia H. Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway. Exp Ther Med. 2020;19(3):1878–86.
89.
go back to reference Feng Y, Pathria G, Heynen-Genel S, Jackson M, James B, Yin J, et al. Identification and characterization of IMD-0354 as a glutamine carrier protein inhibitor in melanoma. Mol Cancer Ther. 2021;20(5):816–32.CrossRef Feng Y, Pathria G, Heynen-Genel S, Jackson M, James B, Yin J, et al. Identification and characterization of IMD-0354 as a glutamine carrier protein inhibitor in melanoma. Mol Cancer Ther. 2021;20(5):816–32.CrossRef
90.
go back to reference Lai M, La Rocca V, Amato R, Freer G, Pistello M. Sphingolipid/ceramide pathways and autophagy in the onset and progression of melanoma: novel therapeutic targets and opportunities. Int J Mol Sci. 2019;20(14). Lai M, La Rocca V, Amato R, Freer G, Pistello M. Sphingolipid/ceramide pathways and autophagy in the onset and progression of melanoma: novel therapeutic targets and opportunities. Int J Mol Sci. 2019;20(14).
91.
go back to reference Allavena G, Del Bello B, Tini P, Volpi N, Valacchi G, Miracco C, et al. Trehalose inhibits cell proliferation and amplifies long-term temozolomide- and radiation-induced cytotoxicity in melanoma cells: a role for autophagy and premature senescence. J Cell Physiol. 2019;234(7):11708–21.CrossRef Allavena G, Del Bello B, Tini P, Volpi N, Valacchi G, Miracco C, et al. Trehalose inhibits cell proliferation and amplifies long-term temozolomide- and radiation-induced cytotoxicity in melanoma cells: a role for autophagy and premature senescence. J Cell Physiol. 2019;234(7):11708–21.CrossRef
92.
go back to reference Taskaeva I, Gogaeva I, Shatruk A, Bgatova N. Lithium enhances autophagy and cell death in skin melanoma: an ultrastructural and immunohistochemical study. Microsc Microanal. 2022;1-9. Taskaeva I, Gogaeva I, Shatruk A, Bgatova N. Lithium enhances autophagy and cell death in skin melanoma: an ultrastructural and immunohistochemical study. Microsc Microanal. 2022;1-9.
93.
go back to reference Li K, Zhang TT, Hua F, Hu ZW. Metformin reduces TRIB3 expression and restores autophagy flux: an alternative antitumor action. Autophagy. 2018;14(7):1278–9.CrossRef Li K, Zhang TT, Hua F, Hu ZW. Metformin reduces TRIB3 expression and restores autophagy flux: an alternative antitumor action. Autophagy. 2018;14(7):1278–9.CrossRef
94.
go back to reference Islam A, Hsieh PF, Liu PF, Chou JC, Liao JW, Hsieh MK, et al. Capsaicin exerts therapeutic effects by targeting tNOX-SIRT1 axis and augmenting ROS-dependent autophagy in melanoma cancer cells. Am J Cancer Res. 2021;11(9):4199–219. Islam A, Hsieh PF, Liu PF, Chou JC, Liao JW, Hsieh MK, et al. Capsaicin exerts therapeutic effects by targeting tNOX-SIRT1 axis and augmenting ROS-dependent autophagy in melanoma cancer cells. Am J Cancer Res. 2021;11(9):4199–219.
95.
go back to reference Hagstrom A, Kal Omar R, Williams PA, Stalhammar G. The rationale for treating uveal melanoma with adjuvant melatonin: a review of the literature. BMC Cancer. 2022;22(1):398.CrossRef Hagstrom A, Kal Omar R, Williams PA, Stalhammar G. The rationale for treating uveal melanoma with adjuvant melatonin: a review of the literature. BMC Cancer. 2022;22(1):398.CrossRef
96.
go back to reference Silvente-Poirot S, Segala G, Poirot MC, Poirot M. Ligand-dependent transcriptional induction of lethal autophagy: a new perspective for cancer treatment. Autophagy. 2018;14(3):555–7.CrossRef Silvente-Poirot S, Segala G, Poirot MC, Poirot M. Ligand-dependent transcriptional induction of lethal autophagy: a new perspective for cancer treatment. Autophagy. 2018;14(3):555–7.CrossRef
97.
go back to reference Armstrong JL, Hill DS, McKee CS, Hernandez-Tiedra S, Lorente M, Lopez-Valero I, et al. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Invest Dermatol. 2015;135(6):1629–37.CrossRef Armstrong JL, Hill DS, McKee CS, Hernandez-Tiedra S, Lorente M, Lopez-Valero I, et al. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Invest Dermatol. 2015;135(6):1629–37.CrossRef
98.
go back to reference Kretschmer N, Deutsch A, Durchschein C, Rinner B, Stallinger A, Higareda-Almaraz JC, et al. Comparative gene expression analysis in WM164 melanoma cells revealed that beta-beta-dimethylacrylshikonin leads to ROS generation, loss of mitochondrial membrane potential, and autophagy induction. Molecules. 2018;23(11). Kretschmer N, Deutsch A, Durchschein C, Rinner B, Stallinger A, Higareda-Almaraz JC, et al. Comparative gene expression analysis in WM164 melanoma cells revealed that beta-beta-dimethylacrylshikonin leads to ROS generation, loss of mitochondrial membrane potential, and autophagy induction. Molecules. 2018;23(11).
99.
go back to reference Wang X, Li X, Xia Y, Wang D, Li X, Liu L, et al. Hernandezine regulates proliferation and autophagy-induced apoptosis in melanoma cells. J Nat Prod. 2022;85(5):1351–62.CrossRef Wang X, Li X, Xia Y, Wang D, Li X, Liu L, et al. Hernandezine regulates proliferation and autophagy-induced apoptosis in melanoma cells. J Nat Prod. 2022;85(5):1351–62.CrossRef
Metadata
Title
Autophagy Paradox: Strategizing Treatment Modality in Melanoma
Authors
Christian Pangilinan, PhD
Xiaowei Xu, MD, PhD
Meenhard Herlyn, DVM, DSc
Chengyu Liang, MD, PhD
Publication date
21-01-2023
Publisher
Springer US
Published in
Current Treatment Options in Oncology / Issue 2/2023
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-023-01053-8

Other articles of this Issue 2/2023

Current Treatment Options in Oncology 2/2023 Go to the issue

Leukemia (PH Wiernik, Section Editor)

New Treatments for Myelofibrosis

Lower Gastrointestinal Cancers (AB Benson, Section Editor)

ctDNA to Guide Treatment of Colorectal Cancer: Ready for Standard of Care?

Palliative and Supportive Care (J Hardy, Section Editor)

Management of Fatigue in Patients with Advanced Cancer

Upper Gastrointestinal Cancers (JD Berlin, Section Editor)

Surgery Matters: Progress in Surgical Management of Gastric Cancer

Live Webinar | 01-10-2024 | 12:30 (CEST)

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live: Tuesday 1st October 2024, 12:30-14:00 (CEST)

In this live webinar, Professor Martin Dreyling and an esteemed, international panel of CAR-T experts will discuss the very latest data on the safety, efficacy and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL, as presented at ASH 2023, EU CAR-T 2024, and EHA 2024. 

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by: Novartis Pharma AG

Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare