REFERENCES
3. Bukavina L, Bensalah K, Bray F, et al. Epidemiology of renal cell carcinoma: 2022 update. Eur Urol. 2022;82:529-42.
5. Usher-Smith J, Simmons RK, Rossi SH, Stewart GD. Current evidence on screening for renal cancer. Nat Rev Urol. 2020;17:637-42.
6. Rizzo M, Pezzicoli G, Tibollo V, Premoli A, Quaglini S. Clinical outcome predictors for metastatic renal cell carcinoma: a retrospective multicenter real-life case series.
7. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008;34:193-205.
8. Ali O, Fishman EK, Kawamoto S. Recurrent renal cell carcinoma following nephrectomy and ablation therapy: radiology perspective. Eur J Radiol. 2018;107:134-42.
10. Jonasch E, Walker CL, Rathmell WK. Clear cell renal cell carcinoma ontogeny and mechanisms of lethality. Nat Rev Nephrol. 2021;17:245-61.
11. Cotta BH, Choueiri TK, Cieslik M, et al. Current landscape of genomic biomarkers in clear cell renal cell carcinoma. Eur Urol. 2023;84:166-75.
12. Rathmell WK, Rumble RB, Van Veldhuizen PJ, et al. Management of metastatic clear cell renal cell carcinoma: ASCO guideline. J Clin Oncol. 2022;40:2957-95.
13. Barragan-Carrillo R, Saad E, Saliby RM, et al. First and second-line treatments in metastatic renal cell carcinoma. Eur Urol. 2025;87:143-54.
14. Zhao Y, Bilal M, Raza A, et al. Tyrosine kinase inhibitors and their unique therapeutic potentialities to combat cancer. Int J Biol Macromol. 2021;168:22-37.
15. Sharma R, Kadife E, Myers M, Kannourakis G, Prithviraj P, Ahmed N. Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma. J Exp Clin Cancer Res. 2021;40:186.
16. Marona P, Górka J, Kwapisz O, et al. Resistance to tyrosine kinase inhibitors promotes renal cancer progression through MCPIP1 tumor-suppressor downregulation and c-Met activation. Cell Death Dis. 2022;13:814.
17. Davis MI, Hunt JP, Herrgard S, et al. Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011;29:1046-51.
18. Liu T, Hwang L, Burley SK, et al. BindingDB in 2024: a FAIR knowledgebase of protein-small molecule binding data. Nucleic Acids Res. 2025;53:D1633-44.
19. Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10:2298-308.
20. Saha D, Ryan KR, Lakkaniga NR, et al. Targeting rearranged during transfection in cancer: a perspective on small-molecule inhibitors and their clinical development. J Med Chem. 2021;64:11747-73.
21. Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008;122:664-71.
22. Karaman MW, Herrgard S, Treiber DK, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008;26:127-32.
24. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003;9:327-37.
25. Wang Y, Liu X, Gong L, et al. Mechanisms of sunitinib resistance in renal cell carcinoma and associated opportunities for therapeutics. Br J Pharmacol. 2023;180:2937-55.
26. Zhou L, Liu XD, Sun M, et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016;35:2687-97.
27. Qu L, Ding J, Chen C, et al. Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell. 2016;29:653-68.
28. Rosenzweig SA. Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem Pharmacol. 2012;83:1041-8.
29. Fukumoto W, Yoshino H, Horike SI, et al. Potential therapeutic target secretogranin II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma. Cancer Sci. 2023;114:3946-56.
30. He H, Li J, Wang W, et al. The SIRT7-mediated deacetylation of CHD1L amplifies HIF-2α-dependent signal that drives renal cell carcinoma progression and sunitinib resistance. Cell Biosci. 2023;13:166.
31. Ge X, Li M, Yin J, et al. Fumarate inhibits PTEN to promote tumorigenesis and therapeutic resistance of type2 papillary renal cell carcinoma. Mol Cell. 2022;82:1249-60.e7.
32. Xiong W, Zhang B, Yu H, Zhu L, Yi L, Jin X. RRM2 regulates sensitivity to sunitinib and PD-1 blockade in renal cancer by stabilizing ANXA1 and activating the AKT pathway. Adv Sci. 2021;8:e2100881.
33. Liu S, Li J, Zhang J, et al. IKBKE regulates renal cell carcinoma progression and sunitinib resistance through the RRM2-AKT pathway. Int J Biol Sci. 2024;20:6146-61.
34. Fang L, Zhang Y, Zang Y, et al. HP-1 inhibits the progression of ccRCC and enhances sunitinib therapeutic effects by suppressing EMT. Carbohydr Polym. 2019;223:115109.
35. Bouchalova P, Beranek J, Lapcik P, et al. Transgelin contributes to a poor response of metastatic renal cell carcinoma to sunitinib treatment. Biomedicines. 2021;9:1145.
36. Xie Y, Shangguan W, Chen Z, et al. Establishment of sunitinib-resistant xenograft model of renal cell carcinoma and the identification of drug-resistant hub genes and pathways. Drug Des Devel Ther. 2021;15:5061-74.
37. Stokes ME, Calvo V, Fujisawa S, et al. PERK inhibition by HC-5404 sensitizes renal cell carcinoma tumor models to antiangiogenic tyrosine kinase inhibitors. Clin Cancer Res. 2023;29:4870-82.
38. Wang Y, Zhang Y, Wang P, Fu X, Lin W. Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy. Mol Cancer. 2020;19:149.
39. Qin S, Wang Y, Wang P, Lv Q. Molecular mechanism of circRNAs in drug resistance in renal cell carcinoma. Cancer Cell Int. 2022;22:369.
40. Huang KB, Pan YH, Shu GN, et al. Circular RNA circSNX6 promotes sunitinib resistance in renal cell carcinoma through the miR-1184/GPCPD1/lysophosphatidic acid axis. Cancer Lett. 2021;523:121-34.
41. Shou Y, Yue C, Wang Q, et al. circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway. Cell Death Dis. 2023;14:232.
42. Liu Y, Chen K, Shou Y, et al. circRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma. Clin Transl Med. 2023;13:e1512.
43. Liu Y, Zhang H, Fang Y, Tang D, Luo Z. Non-coding RNAs in renal cell carcinoma: implications for drug resistance. Biomed Pharmacother. 2023;164:115001.
44. Gao X, Zhang H, Zhang C, et al. The emerging role of long non-coding RNAs in renal cell carcinoma progression and clinical therapy via targeting metabolic regulation. Front Pharmacol. 2023;14:1122065.
45. Pan Y, Lu X, Shu G, et al. Extracellular vesicle-mediated transfer of lncRNA IGFL2-AS1 confers sunitinib resistance in renal cell carcinoma. Cancer Res. 2023;83:103-16.
46. Liu Y, Cheng G, Huang Z, et al. Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma. Cell Death Dis. 2020;11:515.
47. Tian P, Wei J, Li J, Ren J, He C. An oncogenic role of lncRNA SNHG1 promotes ATG7 expression and autophagy involving tumor progression and sunitinib resistance of renal cell carcinoma. Cell Death Discov. 2024;10:273.
48. Pan Y, Liu S, Shu G, et al. STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis. Cell Death Dis. 2025;16:125.
49. He M, Yang H, Shi H, et al. Sunitinib increases the cancer stem cells and vasculogenic mimicry formation via modulating the lncRNA-ECVSR/ERβ/Hif2-α signaling. Cancer Lett. 2022;524:15-28.
50. Azijli K, Gotink KJ, Verheul HM. The potential role of lysosomal sequestration in sunitinib resistance of renal cell cancer. J Kidney Cancer VHL. 2015;2:195-203.
51. Li L, Zhao S, Liu Z, et al. Sunitinib treatment promotes metastasis of drug-resistant renal cell carcinoma via TFE3 signaling pathway. Cell Death Dis. 2021;12:220.
52. Chen WJ, Pan XW, Song X, et al. Preoperative neoadjuvant targeted therapy remodels intra-tumoral heterogeneity of clear-cell renal cell carcinoma and ferroptosis inhibition induces resistance progression. Cancer Lett. 2024;593:216963.
53. Wang Q, Gao S, Shou Y, et al. AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis. Int J Biol Sci. 2023;19:1266-83.
54. Wu J, Wang S, Liu Y, Zhang T, Wang X, Miao C. Integrated single-cell and bulk characterization of cuproptosis key regulator PDHB and association with tumor microenvironment infiltration in clear cell renal cell carcinoma. Front Immunol. 2023;14:1132661.
55. Zeng X, Chen Z, Zhu Y, et al. O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma. Drug Resist Updat. 2024;77:101150.
56. Sato T, Kawasaki Y, Maekawa M, et al. Metabolomic analysis to elucidate mechanisms of sunitinib resistance in renal cell carcinoma. Metabolites. 2020;11:1.
57. Di SC, Chen WJ, Yang W, et al. DEPDC1 as a metabolic target regulates glycolysis in renal cell carcinoma through AKT/mTOR/HIF1α pathway. Cell Death Dis. 2024;15:533.
58. Amaro F, Carvalho M, Bastos ML, Guedes de Pinho P, Pinto J. Metabolomics reveals tyrosine kinase inhibitor resistance-associated metabolic events in human metastatic renal cancer cells. Int J Mol Sci. 2024;25:6328.
59. Wei Z, Cheng G, Ye Y, et al. A fatty acid metabolism signature associated with clinical therapy in clear cell renal cell carcinoma. Front Genet. 2022;13:894736.
60. Liu J, Huang G, Lin H, et al. MTHFD2 enhances cMYC O-GlcNAcylation to promote sunitinib resistance in renal cell carcinoma. Cancer Res. 2025;85:1113-29.
61. Teisseire M, Sahu U, Parola J, et al. De novo serine synthesis is a metabolic vulnerability that can be exploited to overcome sunitinib resistance in advanced renal cell carcinoma. Cancer Res. 2025;85:1857-73.
62. Longo R, D’Andrea MR, Sarmiento R, Salerno F, Gasparini G. Integrated therapy of kidney cancer. Ann Oncol. 2007;18 Suppl 6:vi141-8.
63. Xuan Z, Chen C, Tang W, et al. TKI-resistant renal cancer secretes low-level exosomal miR-549a to induce vascular permeability and angiogenesis to promote tumor metastasis. Front Cell Dev Biol. 2021;9:689947.
64. Gu J, Zhang Y, Han Z, et al. Targeting the ERβ/Angiopoietin-2/Tie-2 signaling-mediated angiogenesis with the FDA-approved anti-estrogen Faslodex to increase the Sunitinib sensitivity in RCC. Cell Death Dis. 2020;11:367.
65. Zhao T, Zhou Y, Wang Q, et al. QPCT regulation by CTCF leads to sunitinib resistance in renal cell carcinoma by promoting angiogenesis. Int J Oncol. 2021;59:48.
66. Chen Y, Lu Z, Qi C, et al. N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma. Mol Cancer. 2022;21:111.
67. Xiong Z, Yuan C, Shi J, et al. Restoring the epigenetically silenced PCK2 suppresses renal cell carcinoma progression and increases sensitivity to sunitinib by promoting endoplasmic reticulum stress. Theranostics. 2020;10:11444-61.
68. Wei Z, Ye Y, Liu C, et al. MIER2/PGC1A elicits sunitinib resistance via lipid metabolism in renal cell carcinoma. J Adv Res. 2025;70:287-305.
69. Liu J, Ren L, Li S, et al. The biology, function, and applications of exosomes in cancer. Acta Pharm Sin B. 2021;11:2783-97.
70. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019;18:75.
71. He J, He J, Min L, et al. Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma. Int J Cancer. 2020;146:1052-63.
72. Lim AR, Vincent BG, Weaver AM, Rathmell WK. Sunitinib and Axitinib increase secretion and glycolytic activity of small extracellular vesicles in renal cell carcinoma. Cancer Gene Ther. 2022;29:683-96.
73. Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol. 2017;14:611-29.
74. Lytle NK, Barber AG, Reya T. Stem cell fate in cancer growth, progression and therapy resistance. Nat Rev Cancer. 2018;18:669-80.
75. Guo C, Sun Y, Zhai W, et al. Hypoxia increases RCC stem cell phenotype via altering the androgen receptor (AR)-lncTCFL5-2-YBX1-SOX2 signaling axis. Cell Biosci. 2022;12:185.
76. Lu J, Li J, Lin Z, et al. Reprogramming of TAMs via the STAT3/CD47-SIRPα axis promotes acquired resistance to EGFR-TKIs in lung cancer. Cancer Lett. 2023;564:216205.
77. Wang S, Rong R, Yang DM, et al. Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer. J Clin Invest. 2023;133:e160330.
78. Shrimali RK, Yu Z, Theoret MR, Chinnasamy D, Restifo NP, Rosenberg SA. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res. 2010;70:6171-80.
79. Puig-Kröger A, Relloso M, Fernández-Capetillo O, et al. Extracellular signal-regulated protein kinase signaling pathway negatively regulates the phenotypic and functional maturation of monocyte-derived human dendritic cells. Blood. 2001;98:2175-82.
80. Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res. 2009;69:2506-13.
81. Ozao-Choy J, Ma G, Kao J, et al. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res. 2009;69:2514-22.
82. Bilen MA, Rini BI, Voss MH, et al. Association of neutrophil-to-lymphocyte ratio with efficacy of first-line avelumab plus axitinib vs. sunitinib in patients with advanced renal cell carcinoma enrolled in the phase 3 JAVELIN renal 101 trial. Clin Cancer Res. 2022;28:738-47.
83. Talmadge JE. Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res. 2007;13:5243-8.
84. Xin S, Su J, Li R, et al. Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells. Sci Rep. 2024;14:13390.
85. Aggen DH, Ager CR, Obradovic AZ, et al. Blocking IL1 beta promotes tumor regression and remodeling of the myeloid compartment in a renal cell carcinoma model: multidimensional analyses. Clin Cancer Res. 2021;27:608-21.
86. Fumarola C, La Monica S, Bonelli M, et al. Immunomodulatory effects of antiangiogenic tyrosine kinase inhibitors in renal cell carcinoma models: impact on following anti-PD-1 treatments. Biochem Pharmacol. 2024;226:116397.
87. Liu W, Ren D, Xiong W, Jin X, Zhu L. A novel FBW7/NFAT1 axis regulates cancer immunity in sunitinib-resistant renal cancer by inducing PD-L1 expression. J Exp Clin Cancer Res. 2022;41:38.
88. Greenberg JW, Kim H, Ahn M, et al. Combination of tipifarnib and sunitinib overcomes renal cell carcinoma resistance to tyrosine kinase inhibitors via tumor-derived exosome and T cell modulation. Cancers. 2022;14:903.
89. Montemagno C, Hagege A, Borchiellini D, et al. Soluble forms of PD-L1 and PD-1 as prognostic and predictive markers of sunitinib efficacy in patients with metastatic clear cell renal cell carcinoma. Oncoimmunology. 2020;9:1846901.
90. Saito S, Yoshino H, Yokoyama S, et al. Targeting heat shock transcription factor 4 enhances the efficacy of cabozantinib and immune checkpoint inhibitors in renal cell carcinoma. Int J Mol Sci. 2025;26:1776.
91. Emanuelli A, Souleyreau W, Chouleur T, et al. Targeting the IL34-CSF1R axis improves metastatic renal cell carcinoma therapy outcome via immune-vascular crosstalk regulation. iScience. 2025;28:112752.
92. Lai Y, Wu W, Liang X, et al. Connexin43 is associated with the progression of clear cell renal carcinoma and is regulated by tangeretin to sygergize with tyrosine kinase inhibitors. Transl Oncol. 2023;35:101712.
93. Yang Y, Fan R, Zhang B, Liu K. COL6A2 in clear cell renal cell carcinoma: a multifaceted driver of tumor progression, immune evasion, and drug sensitivity. J Transl Med. 2025;23:875.
94. Qi Y, Xia Y, Lin Z, et al. Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients. Cancer Immunol Immunother. 2020;69:1565-76.
95. Murakami T, Tanaka N, Takamatsu K, et al. Multiplexed single-cell pathology reveals the association of CD8 T-cell heterogeneity with prognostic outcomes in renal cell carcinoma. Cancer Immunol Immunother. 2021;70:3001-13.
96. Huinen ZR, Huijbers EJM, van Beijnum JR, Nowak-Sliwinska P, Griffioen AW. Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat Rev Clin Oncol. 2021;18:527-40.
97. Nowak-Sliwinska P, van Beijnum JR, Griffioen CJ, et al. Proinflammatory activity of VEGF-targeted treatment through reversal of tumor endothelial cell anergy. Angiogenesis. 2023;26:279-93.
98. Chen Y, McAndrews KM, Kalluri R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol. 2021;18:792-804.
99. Gilkes DM, Semenza GL, Wirtz D. Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer. 2014;14:430-9.
100. Su S, Chen J, Yao H, et al. CD10+GPR77+ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell. 2018;172:841-56.e16.
101. Peng YL, Xiong LB, Zhou ZH, et al. Single-cell transcriptomics reveals a low CD8+ T cell infiltrating state mediated by fibroblasts in recurrent renal cell carcinoma. J Immunother Cancer. 2022;10:e004206.
102. Errarte P, Larrinaga G, López JI. The role of cancer-associated fibroblasts in renal cell carcinoma. An example of tumor modulation through tumor/non-tumor cell interactions. J Adv Res. 2020;21:103-8.
103. Wang Y, Ding W, Hao W, et al. CXCL3/TGF-β-mediated crosstalk between CAFs and tumor cells augments RCC progression and sunitinib resistance. iScience. 2024;27:110224.
104. Chakiryan NH, Kimmel GJ, Kim Y, et al. Geospatial cellular distribution of cancer-associated fibroblasts significantly impacts clinical outcomes in metastatic clear cell renal cell carcinoma. Cancers. 2021;13:3743.
105. Ambrosetti D, Coutts M, Paoli C, et al. Cancer-associated fibroblasts in renal cell carcinoma: implication in prognosis and resistance to anti-angiogenic therapy. BJU Int. 2022;129:80-92.
106. Stupichev D, Miheecheva N, Postovalova E, et al. AI-driven multimodal algorithm predicts immunotherapy and targeted therapy outcomes in clear cell renal cell carcinoma. Cell Rep Med. 2025;6:102299.
107. Li Q, Zeng K, Chen Q, et al. Atractylenolide I inhibits angiogenesis and reverses sunitinib resistance in clear cell renal cell carcinoma through ATP6V0D2-mediated autophagic degradation of EPAS1/HIF2α. Autophagy. 2025;21:619-38.
108. Wang Y, Chen S, Sun S, et al. Wogonin induces apoptosis and reverses sunitinib resistance of renal cell carcinoma cells via inhibiting CDK4-RB pathway. Front Pharmacol. 2020;11:1152.
109. Chiang IC, Chen SY, Hsu YH, Shahidi F, Yen GC. Pterostilbene and 6-shogaol exhibit inhibitory effects on sunitinib resistance and motility by suppressing the RLIP76-initiated Ras/ERK and Akt/mTOR pathways in renal cancer cells. Eur J Pharmacol. 2024;967:176393.
110. Kinoh H, Shibasaki H, Liu X, Yamasoba T, Cabral H, Kataoka K. Nanomedicines blocking adaptive signals in cancer cells overcome tumor TKI resistance. J Control Release. 2020;321:132-44.
111. Azad AK, Zhabyeyev P, Vanhaesebroeck B, et al. Inactivation of endothelial cell phosphoinositide 3-kinase β inhibits tumor angiogenesis and tumor growth. Oncogene. 2020;39:6480-92.
112. Rausch M, Weiss A, Achkhanian J, Rotari A, Nowak-Sliwinska P. Identification of low-dose multidrug combinations for sunitinib-naive and pre-treated renal cell carcinoma. Br J Cancer. 2020;123:556-67.
113. Wu Y, Chen S, Yang X, et al. Combining the tyrosine kinase inhibitor cabozantinib and the mTORC1/2 inhibitor sapanisertib blocks ERK pathway activity and suppresses tumor growth in renal cell carcinoma. Cancer Res. 2023;83:4161-78.
114. Kuroshima K, Yoshino H, Okamura S, et al. Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against sunitinib-resistant renal cell carcinoma. Cancer Sci. 2020;111:1607-18.
115. Liu H, Wang L, Shi X, et al. Calcium saccharate/DUSP6 suppresses renal cell carcinoma glycolytic metabolism and boosts sunitinib efficacy via the ERK-AKT pathway. Biochem Pharmacol. 2024;224:116247.
116. Liu T, Yue X, Chen X, et al. Nilotinib in combination with sunitinib renders MCL-1 for degradation and activates autophagy that overcomes sunitinib resistance in renal cell carcinoma. Cell Oncol. 2024;47:1277-94.
117. Feng C, Kong D, Tong B, et al. Hypoxia-triggered ERRα acetylation enhanced its oncogenic role and promoted progression of renal cell carcinoma by coordinating autophagosome-lysosome fusion. Cell Death Dis. 2025;16:23.
118. Chen Z, Jia X, Cai Y, et al. AUY922 improves sensitivity to sunitinib in clear cell renal cell carcinoma based on network pharmacology and in vitro experiments. Heliyon. 2024;10:e34834.
119. Kamada S, Namekawa T, Ikeda K, et al. Functional inhibition of cancer stemness-related protein DPP4 rescues tyrosine kinase inhibitor resistance in renal cell carcinoma. Oncogene. 2021;40:3899-913.
120. Chen TC, Huang CW, Lo CY, Chen CN, Chang SF, Chen YY. Suppression of SREBP-1 expression by simvastatin decreases visfatin-induced chemoresistance to sunitinib in human renal carcinoma 786-O cells. Life. 2022;12:1890.
121. Khanna P, Soh HJ, Chen CH, et al. ACE2 abrogates tumor resistance to VEGFR inhibitors suggesting angiotensin-(1-7) as a therapy for clear cell renal cell carcinoma. Sci Transl Med. 2021;13:eabc0170.
122. Yin L, Li W, Chen X, et al. HOOK1 inhibits the progression of renal cell carcinoma via TGF-β and TNFSF13B/VEGF-A axis. Adv Sci. 2023;10:e2206955.
123. Lv M, Liu B, Duan Y, et al. Engineered biomimetic nanovesicles synergistically remodel folate-nucleotide and γ-aminobutyric acid metabolism to overcome sunitinib-resistant renal cell carcinoma. ACS Nano. 2024;18:27487-502.
124. Tung MC, Lin YW, Lee WJ, et al. Targeting DRD2 by the antipsychotic drug, penfluridol, retards growth of renal cell carcinoma via inducing stemness inhibition and autophagy-mediated apoptosis. Cell Death Dis. 2022;13:400.
125. Greenberg JW, Kim H, Moustafa AA, et al. Repurposing ketoconazole as an exosome directed adjunct to sunitinib in treating renal cell carcinoma. Sci Rep. 2021;11:10200.
126. Hua Y, Qin M, Lu S, et al. Hyaluronic acid-functionalized MOFs for combined sunitinib and siRNA therapy in renal cell carcinoma. Int J Biol Macromol. 2024;283:137317.
127. Oosterwijk-Wakka JC, de Weijert MCA, Franssen GM, et al. Combination of sunitinib and 177Lu-labeled antibody cG250 targeted radioimmunotherapy: a promising new therapeutic strategy for patients with advanced renal cell cancer. Neoplasia. 2022;32:100826.
128. Oladejo M, Nguyen HM, Silwal A, et al. Listeria-based immunotherapy directed against CD105 exerts anti-angiogenic and anti-tumor efficacy in renal cell carcinoma. Front Immunol. 2022;13:1038807.
129. Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov. 2015;14:111-29.
130. Rawat L, Balan M, Sasamoto Y, Sabarwal A, Pal S. A novel combination therapy with Cabozantinib and Honokiol effectively inhibits c-Met-Nrf2-induced renal tumor growth through increased oxidative stress. Redox Biol. 2023;68:102945.
131. Li J, Tan G, Cai Y, et al. A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET. Biochem Pharmacol. 2021;190:114620.
133. Qian K, Li W, Ren S, et al. HDAC8 enhances the function of HIF-2α by deacetylating ETS1 to decrease the sensitivity of TKIs in ccRCC. Adv Sci. 2024;11:e2401142.
134. Zhang J, Zhang Q, Lin G, et al. Single-cell analysis reveals that vitamin C inhibits bone metastasis of renal cancer via cell cycle arrest and microenvironment remodeling. Adv Sci. 2025;12:e01011.
135. Paz Del Socorro T, Oka K, Boulard O, et al. The biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorγt+Treg and PD-1 blockade efficacy. Gut Microbes. 2024;16:2315631.
136. Barragan-Carrillo R, Saad E, Saliby RM, et al. First and second-line treatments in metastatic renal cell carcinoma. Eur Urol. 2025;87:143-54.
137. Chakraborty S, Balan M, Sabarwal A, Choueiri TK, Pal S. Metabolic reprogramming in renal cancer: events of a metabolic disease. Biochim Biophys Acta Rev Cancer. 2021;1876:188559.
138. Zhang H, Bai L, Wu XQ, et al. Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor. Nat Commun. 2023;14:4274.
139. Meyer ML, Fitzgerald BG, Paz-Ares L, et al. New promises and challenges in the treatment of advanced non-small-cell lung cancer. Lancet. 2024;404:803-22.
140. Zhao Y, He Y, Wang W, et al. Efficacy and safety of immune checkpoint inhibitors for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review, meta-analysis, and network meta-analysis. Lancet Oncol. 2024;25:1347-56.
141. Fu K, Xie F, Wang F, Fu L. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance. J Hematol Oncol. 2022;15:173.
142. Passaro A, Jänne PA, Mok T, Peters S. Overcoming therapy resistance in EGFR-mutant lung cancer. Nat Cancer. 2021;2:377-91.
143. Nagase K, Akutagawa T, Rikitake-Yamamoto M, et al. Cellular and physical microenvironments regulate the aggressiveness and sunitinib chemosensitivity of clear cell renal cell carcinoma. J Pathol. 2021;254:46-56.
144. Bi K, He MX, Bakouny Z, et al. Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma. Cancer Cell. 2021;39:649-61.e5.
145. Quintard C, Tubbs E, Jonsson G, et al. A microfluidic platform integrating functional vascularized organoids-on-chip. Nat Commun. 2024;15:1452.