Itraconazole Reversing Acquired Resistance to Osimertinib in NSCLC by Inhibiting the SHH/DUSP13B/p‐STAT3 Axis
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There is an urgent necessity to devise efficient tactics to tackle the inevitable development of resistance to osimertinib, which is a third‐generation epidermal growth factor receptor (EGFR) inhibitor used in treating EGFR‐mutant nonsmall cell lung cancer (NSCLC). This study demonstrates that combining itraconazole with osimertinib synergistically reduces the proliferation and migration, enhances the apoptosis of osimertinib‐resistant cells, and effectively inhibits the growth of osimertinib‐resistant tumors. Mechanistically, itraconazole combined with osimertinib promotes the proteasomal degradation of sonic hedgehog (SHH), resulting in inactivation of the SHH/Dual‐specificity phosphatase 13B (DUSP13B)/p‐STAT3 and Hedgehog pathways, suppressing Myc proto‐oncogene protein (c‐Myc). Additionally, DUSP13B interacts with signal transducer and activator of transcription 3 (STAT3) and modulates its phosphorylation. Interestingly, it is observed that SHH overexpression partially rescues the synergistic effects of this combination treatment strategy through the SHH/DUSP13B/p‐STAT3 signaling axis. Moreover, it is found that SHH, (GLI1), p‐STAT3, and DUSP13B play significant predictive roles in osimertinib resistance. In lung adenocarcinoma, p‐STAT3 is positively correlated with SHH but negatively correlated with DUSP13B. Together, these results highlight the crucial role of itraconazole in reversing the acquired resistance to osimertinib and provide a scientific rationale for the therapeutic strategy of combining osimertinib with itraconazole.
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DUSP13B modulates STAT3 phosphorylation, and SHH overexpression partially restores resistance, highlighting the central role of itraconazole in reversing acquired osimertinib resistance.
“Mechanistic analyses revealed that DUSP13B modulates STAT3 phosphorylation, and SHH overexpression partially restores resistance, highlighting the central role of ITZ in reversing acquired osimertinib resistance.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [57]
These findings provide a mechanistic rationale for combining itraconazole with osimertinib in resistant non-small cell lung cancer.
“These findings provide a mechanistic rationale for combining ITZ with osimertinib in resistant NSCLC.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [57]
Itraconazole enhances the efficacy of osimertinib in osimertinib-resistant non-small cell lung cancer.
“Zheng, Hongmei, et al.57 demonstrated that ITZ enhances the efficacy of osimertinib in osimertinib-resistant NSCLC.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [57]
The combination of itraconazole and osimertinib inhibited tumor cell proliferation and migration, induced apoptosis, and suppressed tumor growth by promoting proteasomal degradation of sonic hedgehog (SHH), thereby inactivating the SHH/DUSP13B/p-STAT3 and hedgehog pathways and downregulating c-Myc.
“The combination inhibited tumor cell proliferation and migration, induced apoptosis, and suppressed tumor growth by promoting proteasomal degradation of sonic hedgehog (SHH), thereby inactivating the SHH/DUSP13B/p-STAT3 and hedgehog pathways and downregulating c-Myc.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [57]
ITZ has re-sensitized resistance to osimertinib by lung cancer cells via SHH/DUSP13B/p-STAT3 axis inhibition.
“ITZ has also re-sensitized resistance to osimertinib by lung cancer cells via SHH/DUSP13B/p-STAT3 axis inhibition.57”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [57]
ITZ's ability to reverse resistance of lung cancer cells to osimertinib highlights its potential as an adjuvant therapy.
“Moreover, its ability to reverse resistance of lung cancer cells to osimertinib highlights its potential as an adjuvant therapy.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [57]
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Cites
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21660 · Cited by 108,699 · see citing works
Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial
de Koning, H. J., van der Aalst, C. M., de Jong, P. A., Scholten, E. T., Nackaerts, K., Heuvelmans, M. A., Lammers, J.-W. J., Weenink, C., Yousaf-Khan, U., Horeweg, N., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1911793 · Cited by 3,624 · see citing works
Overall Survival with Osimertinib in Untreated, <i>EGFR</i> -Mutated Advanced NSCLC
Ramalingam, S. S., Vansteenkiste, J., Planchard, D., Cho, B. C., Gray, J. E., Ohe, Y., Zhou, C., Reungwetwattana, T., Cheng, Y., Chewaskulyong, B., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1913662 · Cited by 2,914 · see citing works
Levy, J. M. M., Towers, C. G., & Thorburn, A. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.53 · Cited by 2,526 · see citing works
ZDOCK server: interactive docking prediction of protein–protein complexes and symmetric multimers
Pierce, B. G., Wiehe, K. J., Hwang, H., Kim, B., Vreven, T., & Weng, Z. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu097 · Cited by 1,767 · see citing works
Autophagy and autophagy-related proteins in cancer
Li, X., He, S., & Ma, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1138-4 · Cited by 1,653 · see citing works
Shi, Y., Au, J. S. K., Thongprasert, S., Srinivasan, S., Tsai, C., Khoa, M. T., Heeroma, K., Itoh, Y., Cornelio, G. H., & Yang, P. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000033 · Cited by 1,554 · see citing works
Autophagy pathway: Cellular and molecular mechanisms
Yu, L., Chen, Y., & Tooze, S. A. (2017) · Autophagy · doi:10.1080/15548627.2017.1378838 · Cited by 1,488 · see citing works
Jain, A., Lamark, T., Sjøttem, E., Bowitz Larsen, K., Atesoh Awuh, J., Øvervatn, A., McMahon, M., Hayes, J. D., & Johansen, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.118976 · Cited by 1,472 · see citing works
Autophagy and autophagy-related pathways in cancer
Debnath, J., Gammoh, N., & Ryan, K. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00585-z · Cited by 1,443 · see citing works
Autophagy: Regulator of cell death
Liu, S., Yao, S., Yang, H., Liu, S., & Wang, Y. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06154-8 · Cited by 1,193 · see citing works
Monitoring and Measuring Autophagy
Yoshii, S. R., & Mizushima, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091865 · Cited by 1,107 · see citing works
Targeting STAT3 in Cancer Immunotherapy
Zou, S., Tong, Q., Liu, B., Huang, W., Tian, Y., & Fu, X. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01258-7 · Cited by 1,075 · see citing works
Osimertinib with or without Chemotherapy in EGFR -Mutated Advanced NSCLC
Planchard, D., Janne, P. A., Cheng, Y., Yang, J. C., Yanagitani, N., Kim, S., Sugawara, S., Yu, Y., Fan, Y., Geater, S. L., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2306434 · Cited by 772 · see citing works
Pyruvate Kinase M2 Regulates Gene Transcription by Acting as a Protein Kinase
Gao, X., Wang, H., Yang, J. J., Liu, X., & Liu, Z.-R. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.01.001 · Cited by 772 · see citing works
Bugnon, M., Röhrig, U. F., Goullieux, M., Perez, M. A. S., Daina, A., Michielin, O. A., & Zoete, V. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae300 · Cited by 584 · see citing works
Ki-67 protein as a tumour proliferation marker
Menon, S. S., Guruvayoorappan, C., Sakthivel, K. M., & Rasmi, R. R. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.01.011 · Cited by 485 · see citing works
Sequist, L. V. D., Han, J., Ahn, M., Cho, B. C., Yu, H. A., Kim, S.-W., Yang, J. C., Lee, J. S., Su, W., Kowalski, D. M., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30785-5 · Cited by 423 · see citing works
Pasquier, B. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2104-y · Cited by 329 · see citing works
Hedgehog signaling in tissue homeostasis, cancers and targeted therapies
Jing, J., Wu, Z., Wang, J., Luo, G., Lin, H., Fan, Y., & Zhou, C. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01559-5 · Cited by 261 · see citing works
Receptor tyrosine kinase activation: From the ligand perspective
Trenker, R., & Jura, N. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.01.016 · Cited by 224 · see citing works
Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
Chen, H., Chuang, H., & Tan, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112668 · Cited by 205 · see citing works
Olmutinib: First Global Approval
Kim, E. S. (2016) · Drugs · doi:10.1007/s40265-016-0606-z · Cited by 170 · see citing works
p62-mediated phase separation at the intersection of the ubiquitin-proteasome system and autophagy
Danieli, A., & Martens, S. (2018) · Journal of Cell Science · doi:10.1242/jcs.214304 · Cited by 139 · see citing works
Li, Y., Mao, T., Wang, J., Zheng, H., Hu, Z., Cao, P., Yang, S., Zhu, L., Guo, S., Zhao, X., et al. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01082-8 · Cited by 116 · see citing works
Self-citationItraconazole exerts anti-liver cancer potential through the Wnt, PI3K/AKT/mTOR, and ROS pathways
Wang, W., Dong, X., Liu, Y., Ni, B., Sai, N., You, L., Sun, M., Yao, Y., Qu, C., Yin, X., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110661 · Cited by 105 · see citing works
Acquired resistance mechanisms to osimertinib: The constant battle
Zalaquett, Z., Hachem, M. C. R., Kassis, Y., Hachem, S., Eid, R., Kourié, H. R., & Planchard, D. (2023) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2023.102557 · Cited by 97 · see citing works
Hedgehog Signaling: An Achilles’ Heel in Cancer
Niyaz, M., Khan, M. S., & Mudassar, S. (2019) · Translational Oncology · doi:10.1016/j.tranon.2019.07.004 · Cited by 90 · see citing works
Dual-Specificity Phosphatases as Molecular Targets for Inhibition in Human Disease
Ríos, P., Nunes‐Xavier, C. E., Tabernero, L., Köhn, M., & Pulido, R. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5709 · Cited by 83 · see citing works
Bai, X., Zhang, X., Yang, S., An, S., Chen, Z., Su, J., Xie, Z., Gou, L.-Y., & Wu, Y.-L. L. C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149370 · Cited by 73 · see citing works
Raghavan, D., Wheeler, M. S., Doege, D. L., Doty, J. D., Lévy, H. A., Dungan, K., Davis, L. M., Robinson, J. M., Kim, E. S., Mileham, K. F., et al. (2019) · The Oncologist · doi:10.1634/theoncologist.2019-0802 · Cited by 72 · see citing works
Hypoxia-Induced Downregulation of DUSP-2 Phosphatase Drives Colon Cancer Stemness
Hou, P., Li, Y.-H., Lin, S., Lin, S.-C., Lee, J., Lin, B.-W., Liou, J., Chang, J., Kuo, C., Liu, Y.-M., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2990 · Cited by 69 · see citing works
Overcoming cetuximab resistance in HNSCC: The role of AURKB and DUSP proteins
Boeckx, C., de Beeck, K. O., Wouters, A., Deschoolmeester, V., Limame, R., Zwaenepoel, K., Specenier, P. M., Pauwels, P., Vermorken, J. B., Peeters, M., et al. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.08.039 · Cited by 62 · see citing works
Noia, V. D., D’Aveni, A., D’Argento, E., Rossi, S., Ghirardelli, P., Bortolotti, L., Vavassori, V., Bria, E., & Ceresoli, G. L. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100280 · Cited by 60 · see citing works
The MAPK dual specific phosphatase (DUSP) proteins: A versatile wrestler in T cell functionality
Sun, F., Yue, T.-T., Yang, C.-L., Wang, F.-X., Luo, J.-H., Rong, S.-J., Zhang, M., Guo, Y., Xiong, F., & Wang, C.-Y. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107906 · Cited by 59 · see citing works
Self-citationLaface, C., Maselli, F. M., Santoro, A. N., Iaia, M. L., Ambrogio, F., Laterza, M., Guarini, C., Santis, P. D., Perrone, M., & Fedele, P. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15061604 · Cited by 57 · see citing works
Chen, Y., Shen, J., Yuan, M., Li, H., Li, Y., Zheng, S., Han, B., Zhang, C., Liu, S.-L., Sun, Q., et al. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.01.028 · Cited by 56 · see citing works
Li, Y., Zang, H., Qian, G., Owonikoko, T. K., Ramalingam, S. S., & Sun, S. (2019) · Cancer · doi:10.1002/cncr.32655 · Cited by 54 · see citing works
Self-citationMarine Compounds and Cancer: Updates 2020
Dyshlovoy, S. A., & Honecker, F. U. (2020) · Marine Drugs · doi:10.3390/md18120643 · Cited by 53 · see citing works
“Hedgehog pathway”: a potential target of itraconazole in the treatment of cancer
Wei, X., Liu, W., Wang, J. Q., & Tang, Z. (2020) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-019-03117-5 · Cited by 42 · see citing works
Sonic Hedgehog Signaling Pathway in Endothelial Progenitor Cell Biology for Vascular Medicine
Salybekov, A. A., Salybekova, A., Pola, R., & Asahara, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103040 · Cited by 40 · see citing works
Zang, H., Qian, G., Arbiser, J. L., Owonikoko, T. K., Ramalingam, S. S., Fan, S., & Sun, S. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12645 · Cited by 39 · see citing works
Self-citationBai, Z., Ding, N., Ge, J., Wang, Y., Wang, L., Wu, N., Wei, Q., Xu, S., Liu, X., & Zhou, G. (2020) · Cell Biology International · doi:10.1002/cbin.11481 · Cited by 34 · see citing works
Zeng, L., Wang, Z., Liu, X., Zhou, Y., Jin, X., Xiao, Y., Bai, Y., Pan, Y., Zhang, J., & Shao, C. (2023) · Theranostics · doi:10.7150/thno.81999 · Cited by 34 · see citing works
Zhang, W., Bhagwath, A. S., Ramzan, Z., Williams, T. A., Subramaniyan, I., Edpuganti, V., Kallem, R. R., Dunbar, K. B., Ding, P., Gong, K., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0638 · Cited by 33 · see citing works
Yang, Q., Shen, S., Zhou, S., Ni, J., Chen, D.-E., Wang, G., & Li, Y. (2012) · Experimental and molecular pathology (Print) · doi:10.1016/j.yexmp.2012.04.009 · Cited by 30 · see citing works
Hu, H., Zhang, X., Lin, L., Hu, M.-N., Hu, W.-Q., Zhang, J., Miao, X., Yang, W., & Mou, L. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174346 · Cited by 24 · see citing works
Zheng, H., Ning, Y., Zhan, Y., Liu, S., Yang, Y., Wen, Q., & Fan, S. (2021) · Journal of Cancer · doi:10.7150/jca.53119 · Cited by 21 · see citing works
Self-citationChen, J., Shen, Y., Wu, B., Yang, P., Sun, G., Liu, X., Qiang, P., Gao, Y., Sha, F., Li, Z., et al. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01217-9 · Cited by 18 · see citing works
Adjuvant EGFR TKIs in NSCLC harboring EGFR mutations: looking for a consensus way
Attili, I., Passaro, A., Spaggiari, L., Spitaleri, G., & de Marinis, F. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.04.35 · Cited by 10 · see citing works
Selumetinib overcomes gefitinib primary and acquired resistance by regulating MIG6/STAT3 in NSCLC
Song, X., Wang, L., Tang, W., Yuan, L., Liu, Q., Li, J., & Fan, D. (2023) · Archives of Pharmacal Research · doi:10.1007/s12272-023-01471-0 · Cited by 9 · see citing works
Güler, S., Altunok, T. H., Bozkurt, A. S., Zık, B., Asmaz, E. D., KAYAPUNAR, N. V., Sönmez, Ö., Tepedelen, B. E., & Yalçın, A. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.03.090 · Cited by 9 · see citing works
Kamga, P. T., Swalduz, A., Costantini, A., Julié, C., Emile, J., Pérol, M., Avrillon, V., Ortiz‐Cuaran, S., Saintigny, P., & Leprieur, E. G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.747692 · Cited by 5 · see citing works
Kim, J. E., Kim, H., Choe, J., Sun, P., Jheon, S., & Chung, J.-H. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-013-3060-0 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 57
- [1]H. Sung, J. Ferlay, R. L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, CA. Cancer. J. Clin. 2021, 71, 209. 33538338
- [2]H. J. de Koning, C. M. van der Aalst, P. A. de Jong, E. T. Scholten, K. Nackaerts, M. A. Heuvelmans, J.‐W. J. Lammers, C. Weenink, U. Yousaf‐Khan, N. Horeweg, S. van 't Westeinde, M. Prokop, W. P. Mali, F. A. A. Mohamed Hoesein, P. M. A. van Ooijen, J. G. J. V. Aerts, M. A. den Bakker, E. Thunnissen, J. Verschakelen, R. Vliegenthart, J. E. Walter, K. ten Haaf, H. J. M. Groen, M. Oudkerk, N. Engl. J. Med. 2020, 382, 503. 31995683
- [3]D. Raghavan, M. Wheeler, D. Doege, J. D. Doty, H. Levy, K. A. Dungan, L. M. Davis, J. M. Robinson, E. S. Kim, K. F. Mileham, J. Oliver, D. Carrizosa, Oncologist 2020, 25, e777. 31771991 PMC7216453
- [4]I. Attili, A. Passaro, L. Spaggiari, G. Spitaleri, F. de Marinis, Ann. Transl. Med. 2020, 8, 1111. 33145330 PMC7575955
- [5]C. Laface, F. M. Maselli, A. N. Santoro, M. L. Iaia, F. Ambrogio, M. Laterza, C. Guarini, P. De Santis, M. Perrone, P. Fedele, Pharmaceutics 2023, 15, 1604. 37376053 PMC10302309
- [6]D. Planchard, P. A. Jänne, Y. Cheng, J. C.‐H. Yang, N. Yanagitani, S.‐W. Kim, S. Sugawara, Y. Yu, Y. Fan, S. L. Geater, K. Laktionov, C. K. Lee, N. Valdiviezo, S. Ahmed, J.‐M. Maurel, I. Andrasina, J. Goldman, D. Ghiorghiu, Y. Rukazenkov, A. Todd, K. Kobayashi, N. Engl. J. Med. 2023, 389, 1935. 37937763
- [7]K. I. M. E. S. Olmutinib, Drugs 2016, 76, 1153. 27357069
- [8]Z. Zalaquett, M. Catherine Rita Hachem, Y. Kassis, S. Hachem, R. Eid, H. Raphael Kourie, D. Planchard, Cancer Treat. Rev. 2023, 116, 102557. 37060646
- [9]X. Wei, W. Liu, J. Q. Wang, Z. Tang, J. Cancer Res. Clin. Oncol. 2020, 146, 297. 31960187 PMC11804422
- [10]W. Wang, X. Dong, Y. Liu, B. Ni, N. Sai, L. You, M. Sun, Y. Yao, C. Qu, X. Yin, J. Ni, Biomed. Pharmacother. 2020, 131, 110661. 32942154
- [11]W. Zhang, A. S. Bhagwath, Z. Ramzan, T. A. Williams, I. Subramaniyan, V. Edpuganti, R. R. Kallem, K. B. Dunbar, P. Ding, K. Gong, S. A. Geurkink, M. S. Beg, J. Kim, Q. Zhang, A. A. Habib, S.‐H. Choi, R. Lapsiwala, G. Bhagwath, J. E. Dowell, S. D. Melton, C. Jie, W. C. Putnam, T. H. Pham, D. H. Wang, Mol. Cancer Ther. 2021, 20, 1904. 34376577 PMC8492513
- [12]M. Niyaz, M. S. Khan, S. Mudassar, Transl. Oncol. 2019, 12, 1334. 31352196 PMC6664200
- [13]J. Jing, Z. Wu, J. Wang, G. Luo, H. Lin, Y. Fan, C. Zhou, Signal Transduct. Target. Ther. 2023, 8, 315. 37596267 PMC10439210
- [14]P. Takam Kamga, A. Swalduz, A. Costantini, C. Julié, J.‐F. Emile, M. Pérol, V. Avrillon, S. Ortiz‐Cuaran, P. de Saintigny, E. Giroux‐Leprieur, Front. Oncol. 2021, 11, 747692. 34970481 PMC8712335
- [15]X.‐Y. Bai, X.‐C. Zhang, S.‐Q. Yang, S.‐J. An, Z.‐H. Chen, J. Su, Z. Xie, L.‐Y. Gou, Y.‐L. Wu, PLoS One 2016, 11, e0149370. 26943330 PMC4778934
- [16]S. Zou, Q. Tong, B. Liu, W. Huang, Y. Tian, X. Fu, Mol. Cancer 2020, 19, 145. 32972405 PMC7513516
- [17]X. Gao, H. Wang, J. J. Yang, X. Liu, Z. R. Liu, Mol. Cell 2012, 45, 598. 22306293 PMC3299833
- [18]X. Song, L. Wang, W. Tang, L. Yuan, Q. Liu, J. Li, D. Fan, Arch. Pharm. Res. 2023, 46, 924. 38032449
- [19]H. F. Chen, H. C. Chuang, T. H. Tan, Int. J. Mol. Sci. 2019, 2668, 20.31151270
- [20]S. Guler, T. H. Altunok, A. Sarioglu, B. Zik, D. Asmaz, N. Kayapunar, O. Sonmez, B. E. Tepedelen, A. Yalcin, Biochem. Biophys. Res. Commun. 2022, 606, 35. 35338857
- [21]L. Yu, Y. Chen, S. A., Tooze, Autophagy 2018, 14, 207. 28933638 PMC5902171
- [22]X., Li, S., He, B., Ma, Mol. Cancer 2020, 19, 12. 31969156 PMC6975070
- [23]J. Chen, Y. Shen, B. Wu, P. Yang, G. Sun, X. Liu, P. Qiang, Y. Gao, F. Sha, Z. Li, L. Zhang, Cell Death Discovery 2022, 8, 435. 36316321 PMC9622744
- [24]Z. Bai, N. Ding, J. Ge, Y. Wang, L. Wang, N. Wu, Q. Wei, S. Xu, X. Liu, G. Zhou, Cell Biol. Int. 2021, 45, 177. 33049093
- [25]H. Hu, X.‐W. Zhang, L. Li, M.‐N. Hu, W.‐Q. Hu, J.‐Y. Zhang, X.‐K. Miao, W.‐L. Yang, L.‐Y. Mou, Eur. J. Pharmacol. 2021, 908, 174346. 34270985
- [26]H. Zheng, Y. Ning, Y. Zhan, S. Liu, Y. Yang, Q. Wen, S. Fan, J. Cancer 2021, 12, 2065. 33754005 PMC7974520
- [27]H. Zheng, Y. Zhang, Y. Zhan, S. Liu, J. Lu, Q. Wen, S. Fan, Oncol. Rep. 2019, 42, 2363. 31638235 PMC6859453
- [28]P. Ríos, C. E. Nunes‐Xavier, L. Tabernero, M. Köhn, R. Pulido, Antioxid. Redox. Signal 2014, 20, 2251. 24206177
- [29]B. Pasquier, Cell. Mol. Life Sci. 2016, 73, 985. 26658914 PMC11108294
- [30]Y. Shi, J. S.‐K. Au, S. Thongprasert, S. Srinivasan, C.‐M. Tsai, M. T. Khoa, K. Heeroma, Y. Itoh, G. Cornelio, P.‐C. Yang, J. Thorac. Oncol. 2014, 9, 154. 24419411 PMC4132036
- [31]V. Di Noia, A. D'Aveni, E. D'Argento, S. Rossi, P. Ghirardelli, L. Bortolotti, V. Vavassori, E. Bria, G. L. Ceresoli, ESMO Open 2021, 6, 100280. 34634633 PMC8506968
- [32]S. S. Ramalingam, J. Vansteenkiste, D. Planchard, B. C. Cho, J. E. Gray, Y. Ohe, C. Zhou, T. Reungwetwattana, Y. Cheng, B. Chewaskulyong, R. Shah, M. Cobo, K. H. Lee, P. Cheema, M. Tiseo, T. John, M.‐C. Lin, F. Imamura, T. Kurata, A. Todd, R. Hodge, M. Saggese, Y. Rukazenkov, J.‐C. Soria, N. Engl. J. Med. 2020, 382, 41. 31751012
- [33]Y. Li, T. Mao, J. Wang, H. Zheng, Z. Hu, P. Cao, S. Yang, L. Zhu, S. Guo, X. Zhao, Y. Tian, H. Shen, F. Lin, Cell. Commun. Signal 2023, 21, 71. 37041601 PMC10088170
- [34]L. V. Sequist, J.‐Y. Han, M.‐J. Ahn, B. C. Cho, H. Yu, S.‐W. Kim, J. C.‐H. Yang, J. S. Lee, W.‐C. Su, D. Kowalski, S. Orlov, M. Cantarini, R. B. Verheijen, A. Mellemgaard, L. Ottesen, P. Frewer, X. Ou, G. Oxnard, Lancet Oncol. 2020, 21, 373. 32027846
- [35]H. Zang, G. Qian, J. Arbiser, T. K. Owonikoko, S. S. Ramalingam, S. Fan, S.‐Y. Sun, Mol. Oncol. 2020, 14, 882. 32003107 PMC7138398
- [36]Y. Li, H. Zang, G. Qian, T. K. Owonikoko, S. R. Ramalingam, S.‐Y. Sun, Cancer 2020, 126, 1339. 31821539 PMC7050394
- [37]S. S. Menon, C. Guruvayoorappan, K. M. Sakthivel, R. R. Rasmi, Clin. Chim. Acta 2019, 491, 39. 30653951
- [38]A. A. Salybekov, A. K. Salybekova, R. Pola, T. Asahara, Int. J. Mol. Sci. 2018, 19, 3040. 30301174 PMC6213474
- [39]Q. Yang, S. S. Shen, S. Zhou, J. Ni, D. Chen, G. Wang, Y. Li, Exp. Mol. Pathol. 2012, 93, 227. 22554932
- [40]M. Bugnon, U. F. Rohrig, M. Goullieux, M. A. S. Perez, A. Daina, O. Michielin, V. Zoete, Nucl. Acids Res. 2024, 52, W324. 38686803 PMC11223881
- [41]B. G. Pierce, K. Wiehe, H. Hwang, B.‐H. Kim, T. Vreven, Z. Weng, Bioinformatics 2014, 30, 1771. 24532726 PMC4058926
- [42]P. C. Hou, Y. H. Li, S. C. Lin, S. C. Lin, J. C. Lee, B. W. Lin, J.‐P. Liou, J.‐Y. Chang, C. C. Kuo, Y. M. Liu, H. S. Sun, S. J. Tsai, Cancer Res. 2017, 77, 4305. 28652251
- [43]F. Sun, T.‐T. Yue, C.‐L. Yang, F.‐X. Wang, J.‐H. Luo, S.‐J. Rong, M. Zhang, Y. Guo, F. Xiong, C.‐Y. Wang, Int. Immunopharmacol. 2021, 98, 107906. 34198238
- [44]C. Boeckx, K. O. de Beeck, A. Wouters, V. Deschoolmeester, R. Limame, K. Zwaenepoel, P. Specenier, P. Pauwels, J. B. Vermorken, M. Peeters, G. V. Camp, M. Baay, F. Lardon, Cancer Lett. 2014, 354, 365. 25192874
- [45]T. Kong, A. B. A. Laranjeira, K. Yang, D. A. C. Fisher, L. Yu, L. P. De La Frégonnière, A. Z. Wang, M. B. Ruzinova, J. S. Fowles, M. C. Fulbright, M. J. Cox, H. Celik, G. A. Challen, S. Huang, S. T. Oh, Nat. Cancer 2023, 4, 108. 36581736 PMC11288645
- [46]F. Teng, Z. Xu, J. Chen, G. Zheng, G. Zheng, H. Lv, Y. Wang, L. Wang, X. Cheng, Oncol. Rep. 2018, 40, 1203. 29956792 PMC6072387
- [47]J. Levy, C. G. Towers, A. Thorburn, Nat. Rev. Cancer 2017, 17, 528. 28751651 PMC5975367
- [48]J. Debnath, N. Gammoh, K. M. Ryan, Nat. Rev. Mol. Cell Biol. 2023, 24, 560. 36864290 PMC9980873
- [49]S. A. Dyshlovoy, F. Honecker, Mar. Drugs 2020, 18, 643. 33333876 PMC7765281
- [50]S. R. Yoshii, N. Mizushima, Int. J. Mol. Sci. 2017, 18, 1865. 28846632 PMC5618514
- [51]A. Danieli, S. Martens, J. Cell Sci. 2018, 131, jcs214304. 30287680 PMC7610772
- [52]A. Jain, T. Lamark, E. Sjøttem, K. Bowitz Larsen, J. Atesoh Awuh, A. Øvervatn, M. McMahon, J. D. Hayes, T. Johansen, J. Biol. Chem. 2010, 285, 22576. 20452972 PMC2903417
- [53]S. Liu, S. Yao, H. Yang, S. Liu, Y. Wang, Cell Death Dis. 2023, 14, 648. 37794028 PMC10551038
- [54]Y. Chen, J. Shen, M. Yuan, H. Li, Y. Li, S. Zheng, B. Han, C. Zhang, S. Liu, Q. Sun, J. Wu, J. Adv. Res. 2025, 67, 331. 38295877 PMC11725148
- [55]L. Zeng, W. Zheng, X. Liu, Y. Zhou, X. Jin, Y. Xiao, Y. Bai, Y. Pan, J. Zhang, C. Shao, Theranostics 2023, 13, 3725. 37441590 PMC10334832
- [56]R. Trenker, N. Jura, Curr. Opin. Cell Biol. 2020, 63, 174. 32114309 PMC7813211
- [57]J. E. Kim, H. Kim, J. Y. Choe, P. Sun, S. Jheon, J. H. Chung, Ann. Surg. Oncol. 2013, 20, 755. 23709101
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Self-citation
- Authors
- Zheng, H., Tang, Y., Zang, H., Luo, J., Zhou, H., Zhan, Y., Zou, Y., Wen, Q., Ma, J., & Fan, S.
- Affiliations
- Second Xiangya Hospital of Central South University (CN)
- Central South University (CN)
- Corresponding author
- Fan, Songqing
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2024-12-25
- Volume
- 12
- Issue
- 7
- Pages
- e2409416-e2409416
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC11831513
- OpenAlex
- W4405776183
- Cited by
- 7
- References
- 54
- Citations by year
- 2026: 3 · 2025: 4
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82272722, 81773218, 82102805, 82200019)
- Natural Science Foundation of Hunan Province (2021JJ40890)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- itraconazole, osimertinib, acquired drug resistance, EGFR-mutant non-small cell lung cancer, Sonic hedgehog, STAT3 phosphorylation, c-Myc, Hedgehog signaling, proteasomal degradation, combination therapy, lung adenocarcinoma, Gli1
- MeSH terms
- Proto-Oncogene Mas, Acrylamides, Aniline Compounds, Animals, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Disease Models, Animal, Humans, Indoles, Lung Neoplasms, Pyrimidines, Signal Transduction, Apoptosis, Itraconazole, Drug Resistance, Neoplasm, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Mice, Hedgehog Proteins
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