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Receptor tyrosine kinase inhibitors in cancer

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Abstract

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers.

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References

  1. Cancer [Internet]. World Health Organization (2022). Available from https://www.who.int/news-room/fact-sheets/detail/cancer

  2. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A et al (2021) Cancer statistics for the year 2020: an overview. Int J Cancer 149(4):778–789

    Article  CAS  Google Scholar 

  3. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM (2020) Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health 8(2):e180–e190

    Article  PubMed  Google Scholar 

  4. Sudhesh Dev S, Zainal Abidin SA, Farghadani R, Othman I, Naidu R (2021) Receptor tyrosine kinases and their signaling pathways as therapeutic targets of curcumin in cancer. Front Pharmacol 12:772510

    Article  PubMed  PubMed Central  Google Scholar 

  5. Miraghel SA, Ebrahimi N, Khani L, Mansouri A, Jafarzadeh A, Ahmadi A et al (2021) Crosstalk between non-coding RNAs expression profile, drug resistance and immune response in breast cancer. Pharmacol Res 176:106041

    Article  PubMed  Google Scholar 

  6. Carvalho S, Levi-Schaffer F, Sela M, Yarden Y (2016) Immunotherapy of cancer: from monoclonal to oligoclonal cocktails of anti-cancer antibodies: IUPHAR review 18. Br J Pharmacol 173(9):1407–1424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fleuren EDG, Terry RL, Meyran D, Omer N, Trapani JA, Haber M et al (2021) Enhancing the potential of immunotherapy in paediatric sarcomas: breaking the immunosuppressive barrier with receptor tyrosine kinase inhibitors. Biomedicines. 9(12):1798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu KG, Gupta S, Goel S (2017) Immunotherapy: incorporation in the evolving paradigm of renal cancer management and future prospects. Oncotarget 8(10):17313–17327

    Article  PubMed  Google Scholar 

  9. Abou-Fayçal C, Hatat AS, Gazzeri S, Eymin B (2017) Splice variants of the RTK family: their role in tumour progression and response to targeted therapy. Int J Mol Sci 18(2):383

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wintheiser GA, Silberstein P (2022) Physiology, tyrosine kinase receptors. StatPearls. StatPearls Publishing LLC., Treasure Island (FL)

    Google Scholar 

  11. Moshirfar M, Villarreal A, Ronquillo Y (2022) Tyrosine kinase inhibitor keratitis. StatPearls. StatPearls Publishing, Treasure Island (FL)

    Google Scholar 

  12. Paul MK, Mukhopadhyay AK (2004) Tyrosine kinase–role and significance in cancer. Int J Med Sci 1(2):101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Abella JV, Park M (2009) Breakdown of endocytosis in the oncogenic activation of receptor tyrosine kinases. Am J Physiol Endocrinol Metab 296(5):E973–E984

    Article  CAS  PubMed  Google Scholar 

  14. Zhao Y, Zhang D, Guo Y, Lu B, Zhao ZJ, Xu X et al (2021) Tyrosine kinase ROR1 as a target for anti-cancer therapies. Front Oncol 11:680834

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hubbard SR (1997) Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog. EMBO J 16(18):5572–5581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Karpov OA, Fearnly GW, Smith GA, Kankanala J, McPherson MJ, Tomlinson DC et al (2015) Receptor tyrosine kinase structure and function in health and disease. AIMS Biophys. 2(4):476–502

    Article  CAS  Google Scholar 

  17. Ségaliny AI, Tellez-Gabriel M, Heymann MF, Heymann D (2015) Receptor tyrosine kinases: characterisation, mechanism of action and therapeutic interests for bone cancers. J Bone Oncol 4(1):1–12

    Article  PubMed  PubMed Central  Google Scholar 

  18. Du Z, Lovly CM (2018) Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 17(1):58

    Article  PubMed  PubMed Central  Google Scholar 

  19. O’Bryan JP, Songyang Z, Cantley L, Der CJ, Pawson T (1996) A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is specifically expressed in the brain. Proc Natl Acad Sci USA 93(7):2729–2734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7):1117–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Alexander PB, Wang XF (2015) Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies. Front Med 9(2):134–138

    Article  PubMed  PubMed Central  Google Scholar 

  22. Maruyama IN (2014) Mechanisms of activation of receptor tyrosine kinases: monomers or dimers. Cells 3(2):304–330

    Article  PubMed  PubMed Central  Google Scholar 

  23. Monast C, Mehta N, Lazzara M (2013) Diversity in dimerization topologies enables differential control of receptor tyrosine kinase phosphorylation dynamics. Cell Mol Bioeng. 7:86

    Article  Google Scholar 

  24. Nolen B, Taylor S, Ghosh G (2004) Regulation of protein kinases; controlling activity through activation segment conformation. Mol Cell 15(5):661–675

    Article  CAS  PubMed  Google Scholar 

  25. Niu XL, Peters KG, Kontos CD (2002) Deletion of the carboxyl terminus of Tie2 enhances kinase activity, signaling, and function. Evidence for an autoinhibitory mechanism. J Biol Chem 277(35):31768–31773

    Article  CAS  PubMed  Google Scholar 

  26. Dibb NJ, Dilworth SM, Mol CD (2004) Switching on kinases: oncogenic activation of BRAF and the PDGFR family. Nat Rev Cancer 4(9):718–727

    Article  CAS  PubMed  Google Scholar 

  27. Knowles PP, Murray-Rust J, Kjær S, Scott RP, Hanrahan S, Santoro M et al (2006) Structure and chemical inhibition of the RET tyrosine kinase domain. J Biol Chem 281(44):33577–33587

    Article  CAS  PubMed  Google Scholar 

  28. Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J (2006) An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 125(6):1137–1149

    Article  CAS  PubMed  Google Scholar 

  29. Shibuya M (2011) Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer 2(12):1097–1105

    Article  PubMed  PubMed Central  Google Scholar 

  30. Futami H, Sakai R (2009) RET protein promotes non-adherent growth of NB-39-nu neuroblastoma cell line. Cancer Sci 100(6):1034–1039

    Article  CAS  PubMed  Google Scholar 

  31. Jain S (2009) The many faces of RET dysfunction in kidney. Organogenesis 5(4):177–190

    Article  PubMed  PubMed Central  Google Scholar 

  32. Jeanpierre C, Macé G, Parisot M, Morinière V, Pawtowsky A, Benabou M et al (2011) RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects. J Med Genet 48(7):497–504

    Article  CAS  PubMed  Google Scholar 

  33. Herbst R (2020) MuSK function during health and disease. Neurosci Lett 716:134676

    Article  CAS  PubMed  Google Scholar 

  34. Myers KV, Amend SR, Pienta KJ (2019) Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment. Mol Cancer 18(1):94

    Article  PubMed  PubMed Central  Google Scholar 

  35. Shafit-Zagardo B, Gruber RC, DuBois JC (2018) The role of TAM family receptors and ligands in the nervous system: From development to pathobiology. Pharmacol Ther 188:97–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Artim SC, Kiyatkin A, Lemmon MA (2020) Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB. Biochem J 477(20):4053–4070

    Article  CAS  PubMed  Google Scholar 

  37. Lang SS, Kumar NK, Madsen P, Gajjar AA, Gajjar E, Resnick AC et al (2022) Neurotrophic tyrosine receptor kinase fusion in pediatric central nervous system tumors. Cancer Genet 262–263:64–70

    Article  PubMed  Google Scholar 

  38. Yan D, Earp HS, DeRyckere D, Graham DK (2021) Targeting MERTK and AXL in EGFR mutant non-small cell lung cancer. Cancers 13(22):5639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wium M, Ajayi-Smith AF, Paccez JD, Zerbini LF (2021) The role of the receptor tyrosine kinase Axl in carcinogenesis and development of therapeutic resistance: an overview of molecular mechanisms and future applications. Cancers 13(7):1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhao P, Jiang D, Huang Y, Chen C (2021) EphA2: a promising therapeutic target in breast cancer. J Genet Genomics Yi chuan xue bao 48(4):261–267

    Article  CAS  PubMed  Google Scholar 

  41. Chu M, Li T, Shen B, Cao X, Zhong H, Zhang L et al (2016) Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII. Elife 5:e21032

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wieduwilt M, Moasser M (2008) The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol Life Sci 65(10):1566–1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rothlin CV, Carrera-Silva EA, Bosurgi L, Ghosh S (2015) TAM receptor signaling in immune homeostasis. Annu Rev Immunol 33:355–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Pierce AM, Keating AK (2014) TAM receptor tyrosine kinases: expression, disease and oncogenesis in the central nervous system. Brain Res 1542:206–220

    Article  CAS  PubMed  Google Scholar 

  45. Burden SJ, Yumoto N, Zhang W (2013) The role of MuSK in synapse formation and neuromuscular disease. Cold Spring Harb Perspect Biol 5(5):a009167

    Article  PubMed  PubMed Central  Google Scholar 

  46. Corcoran C, O’Driscoll L (2015) Receptor tyrosine kinases and drug resistance: development and characterization of in vitro models of resistance to RTK inhibitors. Methods Mol Biol (Clifton, NJ) 1233:169–180

    Article  Google Scholar 

  47. Lamorte L, Park M (2001) The receptor tyrosine kinases: role in cancer progression. Surg Oncol Clin N Am 10(2):271–288

    Article  CAS  PubMed  Google Scholar 

  48. Sharma P, Shukla A, Kalani K, Dubey V, Srivastava SK, Luqman S et al (2015) Water molecules increases binding affinity of natural PI3Kγ inhibitors against cancer. Curr Comput Aided Drug Des 11(4):304–320

    Article  CAS  PubMed  Google Scholar 

  49. Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7(3):169–181

    Article  CAS  PubMed  Google Scholar 

  50. Takeuchi K, Ito F (2011) Receptor tyrosine kinases and targeted cancer therapeutics. Biol Pharm Bull 34(12):1774–1780

    Article  CAS  PubMed  Google Scholar 

  51. Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT et al (2012) ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol Off J Am Soc Clin Oncol 30(8):863–870

    Article  CAS  Google Scholar 

  52. Hassanein M, Almahayni MH, Ahmed SO, Gaballa S, El Fakih R (2016) FLT3 Inhibitors for Treating Acute Myeloid Leukemia. Clin Lymphoma Myeloma Leuk 16(10):543–549

    Article  PubMed  Google Scholar 

  53. Kato S, Subbiah V, Marchlik E, Elkin SK, Carter JL, Kurzrock R (2017) RET aberrations in diverse cancers: next-generation sequencing of 4,871 patients. Clin Cancer Res Off J Am Assoc Cancer Res 23(8):1988–1997

    Article  CAS  Google Scholar 

  54. Chew NJ, Nguyen EV, Su SP, Novy K, Chan HC, Nguyen LK et al (2020) FGFR3 signaling and function in triple negative breast cancer. Cell Commun Signal 18(1):13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Adashek JJ, Desai AP, Andreev-Drakhlin AY, Roszik J, Cote GJ, Subbiah V (2021) Hallmarks of RET and co-occuring genomic alterations in RET-aberrant cancers. Mol Cancer Ther 20(10):1769–1776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Regad T, Targeting RTK (2015) Signaling pathways in cancer. Cancers 7(3):1758–1784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chevallier M, Borgeaud M, Addeo A, Friedlaender A (2021) Oncogenic driver mutations in non-small cell lung cancer: past, present and future. World J Clin Oncol 12(4):217–237

    Article  PubMed  PubMed Central  Google Scholar 

  58. Abdel-Rahman WM, Al-Khayyal NA, Nair VA, Aravind SR, Saber-Ayad M (2017) Role of AXL in invasion and drug resistance of colon and breast cancer cells and its association with p53 alterations. World J Gastroenterol 23(19):3440–3448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Taccaliti A, Silvetti F, Palmonella G, Boscaro M (2011) Genetic alterations in medullary thyroid cancer: diagnostic and prognostic markers. Curr Genomics 12(8):618–625

    Article  CAS  Google Scholar 

  60. Mo H-N, Liu P (2017) Targeting MET in cancer therapy. Chronic Dis Transl Med 3(3):148–153

    PubMed  PubMed Central  Google Scholar 

  61. Zhao S, Wu W, Jiang H, Ma L, Pan C, Jin C et al (2021) Selective inhibitor of the c-Met receptor tyrosine kinase in advanced hepatocellular carcinoma: no beneficial effect with the use of tivantinib? Front Immunol 12:731527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Woo HY, Yoo SY, Heo J (2017) New chemical treatment options in second-line hepatocellular carcinoma: what to do when sorafenib fails? Expert Opin Pharmacother 18(1):35–44

    Article  CAS  PubMed  Google Scholar 

  63. Qi X-S, Guo X-Z, Han G-H, Li H-Y, Chen J (2015) MET inhibitors for treatment of advanced hepatocellular carcinoma: a review. World J Gastroenterol: WJG 21(18):5445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Peters S, Adjei AA (2012) MET: a promising anticancer therapeutic target. Nat Rev Clin Oncol 9(6):314–326

    Article  CAS  PubMed  Google Scholar 

  65. Zhou Y, Wang Y, Chen H, Xu Y, Luo Y, Deng Y et al (2021) Immuno-oncology: are TAM receptors in glioblastoma friends or foes? Cell Commun Signal 19(1):11

    Article  PubMed  PubMed Central  Google Scholar 

  66. AbbaspourBabaei M, Kamalidehghan B, Saleem M, Huri HZ, Ahmadipour F (2016) Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des Dev Ther 10:2443–2459

    Article  Google Scholar 

  67. Brizzi MF, Zini MG, Aronica MG, Blechman JM, Yarden Y, Pegoraro L (1994) Convergence of signaling by interleukin-3, granulocyte-macrophage colony-stimulating factor, and mast cell growth factor on JAK2 tyrosine kinase. J Biol Chem 269(50):31680–31684

    Article  CAS  PubMed  Google Scholar 

  68. Zhao Z, Zhao S, Luo L, Xiang Q, Zhu Z, Wang J et al (2021) miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial–mesenchymal transition. Br J Cancer 124(5):982–994

    Article  CAS  PubMed  Google Scholar 

  69. Wiseman SM, Makretsov N, Nielsen TO, Gilks B, Yorida E, Cheang M et al (2005) Coexpression of the type 1 growth factor receptor family members HER-1, HER-2, and HER-3 has a synergistic negative prognostic effect on breast carcinoma survival. Cancer 103(9):1770–1777

    Article  CAS  PubMed  Google Scholar 

  70. Vijapurkar U, Cheng K, Koland JG (1998) Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks heregulin-dependent activation of mitogen-activated protein kinase. J Biol Chem 273(33):20996–21002

    Article  CAS  PubMed  Google Scholar 

  71. Nalwoga H, Arnes JB, Wabinga H, Akslen LA (2008) Expression of EGFR and c-kit is associated with the basal-like phenotype in breast carcinomas of African women. APMIS Acta Pathol Microbiol Immunol Scand 116(6):515–525

    Article  CAS  Google Scholar 

  72. Davol PA, Bagdasaryan R, Elfenbein GJ, Maizel AL, Frackelton AR Jr (2003) Shc proteins are strong, independent prognostic markers for both node-negative and node-positive primary breast cancer. Can Res 63(20):6772–6783

    CAS  Google Scholar 

  73. Ursini-Siegel J, Cory S, Zuo D, Hardy WR, Rexhepaj E, Lam S et al (2010) Receptor tyrosine kinase signaling favors a protumorigenic state in breast cancer cells by inhibiting the adaptive immune response. Can Res 70(20):7776–7787

    Article  CAS  Google Scholar 

  74. Ayoub NM, Alkhalifa AE, Ibrahim DR, Alhusban A (2021) Combined crizotinib and endocrine drugs inhibit proliferation, migration, and colony formation of breast cancer cells via downregulation of MET and estrogen receptor. Med Oncol (Northwood, Lond, Engl) 38(1):8

    Article  CAS  Google Scholar 

  75. Imura Y, Yasui H, Outani H, Wakamatsu T, Hamada K, Nakai T et al (2014) Combined targeting of mTOR and c-MET signaling pathways for effective management of epithelioid sarcoma. Mol Cancer 13:185

    Article  PubMed  PubMed Central  Google Scholar 

  76. Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F et al (2015) Phase III multinational, randomized, double-blind, placebo-controlled study of tivantinib (ARQ 197) plus erlotinib versus erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol 33(24):2667–2674

    Article  CAS  Google Scholar 

  77. Xu L, Kikuchi E, Xu C, Ebi H, Ercan D, Cheng KA et al (2012) Combined EGFR/MET or EGFR/HSP90 inhibition is effective in the treatment of lung cancers codriven by mutant EGFR containing T790M and MET. Can Res 72(13):3302–3311

    Article  CAS  Google Scholar 

  78. Haddley K (2013) Trastuzumab emtansine for the treatment of HER2-positive metastatic breast cancer. Drugs Today (Barcelona, Spain, 1998) 49(11):701–715

    Article  CAS  Google Scholar 

  79. Mendes D, Alves C, Afonso N, Cardoso F, Passos-Coelho JL, Costa L et al (2015) The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer—a systematic review. Breast Cancer Res 17:140

    Article  PubMed  PubMed Central  Google Scholar 

  80. Zhang Y (2021) The root cause of drug resistance in HER2-positive breast cancer and the therapeutic approaches to overcoming the resistance. Pharmacol Ther 218:107677

    Article  CAS  PubMed  Google Scholar 

  81. Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360(14):1408–1417

    Article  PubMed  Google Scholar 

  82. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M et al (2014) Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol 25(7):1346–1355

    Article  CAS  Google Scholar 

  83. Zhang Q, Xiao H, Jin F, Li M, Luo J, Wang G (2018) Cetuximab improves AZD6244 antitumor activity in colorectal cancer HT29 cells in vitro and in nude mice by attenuating HER3/Akt pathway activation. Oncol Lett 16(1):326–334

    PubMed  PubMed Central  Google Scholar 

  84. Chan MM, Sjoquist KM, Zalcberg JR (2015) Clinical utility of ramucirumab in advanced gastric cancer. Biol Targets Therapy 9:93–105

    CAS  Google Scholar 

  85. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C et al (2014) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet (Lond, Engl) 383(9911):31–39

    Article  CAS  Google Scholar 

  86. Zheng Q, Dong H, Mo J, Zhang Y, Huang J, Ouyang S et al (2021) A novel STAT3 inhibitor W2014-S regresses human non-small cell lung cancer xenografts and sensitizes EGFR-TKI acquired resistance. Theranostics 11(2):824–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lai YL, Wang KH, Hsieh HP, Yen WC (2022) Novel FLT3/AURK multikinase inhibitor is efficacious against sorafenib-refractory and sorafenib-resistant hepatocellular carcinoma. J Biomed Sci 29(1):5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Chang CH, Lee CH, Ko JC, Chang LY, Lee MC, Wang JY et al (2017) Gefitinib or erlotinib in previously treated non-small-cell lung cancer patients: a cohort study in Taiwan. Cancer Med 6(7):1563–1572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kim YJ, Oremus M, Chen HH, McFarlane T, Fearon D, Horton S (2021) Cost-effectiveness analysis of afatinib, erlotinib, and gefitinib as first-line treatments for EGFR mutation-positive non-small-cell lung cancer in Ontario, Canada. Pharmacoeconomics 39(5):537–548

    Article  PubMed  Google Scholar 

  90. Zhang LD, Gao H, Qin SM, Zeng Q, Chen QF (2022) Osimertinib is an effective epidermal growth factor receptor-tyrosine kinase inhibitor choice for lung cancer with epidermal growth factor receptor exon 18–25 kinase domain duplication: report of two cases. Anticancer Drugs 33(1):e486–e490

    Article  CAS  PubMed  Google Scholar 

  91. Yoshimatsu Y, Ebi N, Ooi R, Sueyasu T, Nishizawa S, Munechika M et al (2021) Osimertinib for lung squamous cell carcinoma: a case report and literature review. Intern Med (Tokyo, Jpn) 60(7):1067–1071

    Article  Google Scholar 

  92. Knetki-Wróblewska M, Kowalski DM, Czyżewicz G, Bryl M, Wrona A, Dziadziuszko R et al (2020) Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice—the Expanded Drug Access Program in Poland. Adv Respir Med 88(3):189–196

    Article  PubMed  Google Scholar 

  93. Padda SK, Reckamp KL, Koczywas M, Neal JW, Kawashima J, Kong S et al (2022) A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer. Cancer Chemother Pharmacol 89(1):105–115

    Article  CAS  PubMed  Google Scholar 

  94. Zhang Y, Zhang Y, Niu W, Ge X, Li X, Fan F et al (2021) Effect of almonertinib on the proliferation, invasion, and migration in non-small cell lung cancer cells. Zhong nan da xue xue bao Yi xue ban J Central South Univ Med Sci 46(10):1045–1053

    Google Scholar 

  95. Gregorc V, Lazzari C, Karachaliou N, Rosell R, Santarpia M (2018) Osimertinib in untreated epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer. Transl Lung Cancer Res 7(Suppl 2):S165–S170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Awada A, Berghmans T, Clement PM, Cuppens K, De Wilde B, Machiels JP et al (2022) Belgian expert consensus for tumor-agnostic treatment of NTRK gene fusion-driven solid tumors with larotrectinib. Crit Rev Oncol Hematol 169:103564

    Article  PubMed  Google Scholar 

  97. Awada A, Saliba W, Bozovic-Spasojevic I (2011) Lapatinib ditosylate: expanding therapeutic options for receptor tyrosine-protein kinase erbB-2-positive breast cancer. Drugs Today (Barcelona, Spain, 1998) 47(5):335–345

    Article  CAS  Google Scholar 

  98. Ai B, Yang Y (2020) [Progress of bevacizumab in the front-line treatment of advanced non-small cell lung cancer]. Zhongguo fei ai za zhi Chinese J Lung Cancer 23(7):626–630

    Google Scholar 

  99. Nome ME, Euceda LR, Jabeen S, Debik J, Bathen TF, Giskeødegård GF et al (2020) Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers. Int J Cancer 146(1):223–235

    Article  CAS  PubMed  Google Scholar 

  100. Yu Z, Du J, Hui H, Kan S, Huo T, Zhao K et al (2021) LT-171-861, a novel FLT3 inhibitor, shows excellent preclinical efficacy for the treatment of FLT3 mutant acute myeloid leukemia. Theranostics 11(1):93–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Weisberg E, Sattler M, Manley PW, Griffin JD (2018) Spotlight on midostaurin in the treatment of FLT3-mutated acute myeloid leukemia and systemic mastocytosis: design, development, and potential place in therapy. Onco Targets Ther 11:175–182

    Article  PubMed  Google Scholar 

  102. Krayem M, Aftimos P, Najem A, van den Hooven T, van den Berg A, Hovestad-Bijl L et al (2020) Kinome profiling to predict sensitivity to MAPK inhibition in melanoma and to provide new insights into intrinsic and acquired mechanism of resistance. Cancers 12(2):512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Miao B, Ji Z, Tan L, Taylor M, Zhang J, Choi HG et al (2015) EPHA2 is a mediator of vemurafenib resistance and a novel therapeutic target in melanoma. Cancer Discov 5(3):274–287

    Article  CAS  PubMed  Google Scholar 

  104. Das I, Gad H, Bräutigam L, Pudelko L, Tuominen R, Höiom V et al (2020) AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma. Cell Death Differ 27(7):2081–2098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Boshuizen J, Pencheva N, Krijgsman O, Altimari DD, Castro PG, de Bruijn B et al (2021) Cooperative targeting of immunotherapy-resistant melanoma and lung cancer by an AXL-targeting antibody-drug conjugate and immune checkpoint blockade. Can Res 81(7):1775–1787

    Article  CAS  Google Scholar 

  106. Zhou K, Cai X, Wang X, Lan X, Zhang X (2022) Efficacy and safety of WBRT+EGFR-TKI versus WBRT only in the treatment of NSCLC patients with brain metastasis: an updated meta-analysis. Thoracic Cancer 13(4):563–570

    Article  CAS  PubMed  Google Scholar 

  107. Tan HY, Wang N, Lam W, Guo W, Feng Y, Cheng YC (2018) Targeting tumour microenvironment by tyrosine kinase inhibitor. Mol Cancer 17(1):43

    Article  PubMed  PubMed Central  Google Scholar 

  108. Garner H, de Visser KE (2020) Immune crosstalk in cancer progression and metastatic spread: a complex conversation. Nat Rev Immunol 20(8):483–497

    Article  CAS  PubMed  Google Scholar 

  109. Labani-Motlagh A, Ashja-Mahdavi M, Loskog A (2020) The tumor microenvironment: a milieu hindering and obstructing antitumor immune responses. Front Immunol 11:940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Gaspar N, Venkatramani R, Hecker-Nolting S, Melcon SG, Locatelli F, Bautista F et al (2021) Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study. Lancet Oncol 22(9):1312–1321

    Article  CAS  PubMed  Google Scholar 

  111. Italiano A, Mir O, Mathoulin-Pelissier S, Penel N, Piperno-Neumann S, Bompas E et al (2020) Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol 21(3):446–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Tang L, Niu X, Wang Z, Cai Q, Tu C, Fan Z et al (2022) Anlotinib for recurrent or metastatic primary malignant bone tumor: a multicenter, single-arm trial. Front Oncol 12:811687

    Article  PubMed  PubMed Central  Google Scholar 

  113. Lu X, Horner JW, Paul E, Shang X, Troncoso P, Deng P et al (2017) Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543(7647):728–732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Bergerot P, Lamb P, Wang E, Pal SK (2019) Cabozantinib in combination with immunotherapy for advanced renal cell carcinoma and urothelial carcinoma: rationale and clinical evidence. Mol Cancer Ther 18(12):2185–2193

    Article  CAS  PubMed  Google Scholar 

  115. Patnaik A, Swanson KD, Csizmadia E, Solanki A, Landon-Brace N, Gehring MP et al (2017) Cabozantinib eradicates advanced murine prostate cancer by activating antitumor innate immunity. Cancer Discov 7(7):750–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Fu Y, Peng Y, Zhao S, Mou J, Zeng L, Jiang X et al (2021) Combination foretinib and anti-PD-1 antibody immunotherapy for colorectal carcinoma. Front Cell Dev Biol 9:689727

    Article  PubMed  PubMed Central  Google Scholar 

  117. Chong CR, Jänne PA (2013) The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med 19(11):1389–1400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Wium M, Ajayi-Smith AF, Paccez JD, Zerbini LF (2021) The role of the receptor tyrosine kinase Axl in carcinogenesis and development of therapeutic resistance: an overview of molecular mechanisms and future applications. Cancers 13(7):1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Rosenzweig SA (2018) Acquired resistance to drugs targeting tyrosine kinases. Adv Cancer Res 138:71–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B (2017) The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull 7(3):339–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Shaikh M, Shinde Y, Pawara R, Noolvi M, Surana S, Ahmad I et al (2022) Emerging approaches to overcome acquired drug resistance obstacles to osimertinib in non-small-cell lung cancer. J Med Chem 65(2):1008–1046

    Article  CAS  PubMed  Google Scholar 

  122. Deininger M, Buchdunger E, Druker BJ (2005) The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 105(7):2640–2653

    Article  CAS  PubMed  Google Scholar 

  123. He C, Wang Y (2022) Role of the EGFR-KDD mutation as a possible mechanism of acquired resistance of non-small cell lung cancer to EGFR tyrosine kinase inhibitors: a case report. Mol Clin Oncol 16(2):30

    Article  PubMed  Google Scholar 

  124. Xiu W, Zhang Q, Yu M, Huang Y, Huang M (2021) Case report: outcome of osimertinib treatment in lung adenocarcinoma patients with acquired KRAS mutations. Front Oncol 11:630256

    Article  PubMed  PubMed Central  Google Scholar 

  125. Liu S, Jiang Z, Xiao P, Li X, Chen Y, Tang H et al (2022) Hsa_circ_0005576 promotes osimertinib resistance through the miR-512-5p/IGF1R axis in lung adenocarcinoma cells. Cancer Sci 113(1):79–90

    Article  CAS  PubMed  Google Scholar 

  126. Qu F, Zhou Y, Yu W (2022) A review of research progress on mechanisms and overcoming strategies of acquired osimertinib resistance. Anticancer Drugs 33(1):e76–e83

    Article  CAS  PubMed  Google Scholar 

  127. Takano N, Seike M, Sugano T, Matsuda K, Hisakane K, Yoshikawa A et al (2022) A novel molecular target in EGFR-mutant lung cancer treated with the combination of osimertinib and pemetrexed. Anticancer Res 42(2):709–722

    Article  CAS  PubMed  Google Scholar 

  128. Yiming R, Takeuchi Y, Nishimura T, Li M, Wang Y, Meguro-Horike M et al (2021) MUSASHI-2 confers resistance to third-generation EGFR-tyrosine kinase inhibitor osimertinib in lung adenocarcinoma. Cancer Sci 112(9):3810–3821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Cascone T, Sacks RL, Subbiah IM, Drobnitzky N, Piha-Paul SA, Hong DS et al (2021) Safety and activity of vandetanib in combination with everolimus in patients with advanced solid tumors: a phase I study. ESMO Open 6(2):100079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol 27(22):3584–3590

    Article  CAS  Google Scholar 

  131. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M et al (2009) Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol Off J Am Soc Clin Oncol 27(20):3312–3318

    Article  CAS  Google Scholar 

  132. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15(3):232–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Piao Y, Liang J, Holmes L, Henry V, Sulman E, de Groot JF (2013) Acquired resistance to anti-VEGF therapy in glioblastoma is associated with a mesenchymal transition. Clin Cancer Res Off J Am Assoc Cancer Res 19(16):4392–4403

    Article  CAS  Google Scholar 

  134. Simon T, Gagliano T, Giamas G (2017) Direct effects of anti-angiogenic therapies on tumor cells: VEGF signaling. Trends Mol Med 23(3):282–292

    Article  CAS  PubMed  Google Scholar 

  135. Uribesalgo I, Hoffmann D, Zhang Y, Kavirayani A, Lazovic J, Berta J et al (2019) Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy. EMBO Mol Med 11(8):e9266

    Article  PubMed  PubMed Central  Google Scholar 

  136. Sounni NE, Cimino J, Blacher S, Primac I, Truong A, Mazzucchelli G et al (2014) Blocking lipid synthesis overcomes tumor regrowth and metastasis after antiangiogenic therapy withdrawal. Cell Metab 20(2):280–294

    Article  CAS  PubMed  Google Scholar 

  137. Srivastava A, Srivastava P, Mathur S, Abbas S, Rai N, Tiwari S et al (2022) Lipid metabolism and mitochondria: cross talk in cancer. Curr Drug Targets 23(6):606–627

    Article  PubMed  Google Scholar 

  138. Wang H, Xi Q, Wu G (2016) Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway. Cancer Med 5(7):1599–1606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Yasumoto Y, Miyazaki H, Vaidyan LK, Kagawa Y, Ebrahimi M, Yamamoto Y et al (2016) Inhibition of fatty acid synthase decreases expression of stemness markers in glioma stem cells. PLoS ONE 11(1):e0147717

    Article  PubMed  PubMed Central  Google Scholar 

  140. Ahmad I, Mui E, Galbraith L, Patel R, Tan EH, Salji M et al (2016) Sleeping beauty screen reveals Pparg activation in metastatic prostate cancer. Proc Natl Acad Sci USA 113(29):8290–8295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Wang S, Liu C, Lei Q, Wu Z, Miao X, Zhu D et al (2021) Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells. Respir Res 22(1):146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Satoh H, Kagohashi K (2022) Response to erlotinib and bevacizumab combination therapy after acquired resistance to osimertinib in patients with non-small cell lung cancer. Anticancer Drugs 33(3):320–322

    Article  CAS  PubMed  Google Scholar 

  143. Scherschinski L, Prem M, Kremenetskaia I, Tinhofer I, Vajkoczy P, Karbe AG et al (2022) Regulation of the receptor tyrosine kinase AXL in response to therapy and its role in therapy resistance in glioblastoma. Int J Mol Sci 23(2):982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Xia L, Peng J, Lou G, Pan M, Zhou Q, Hu W et al (2022) Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study. J Immunother Cancer. 10(1):e003831

    Article  PubMed  PubMed Central  Google Scholar 

  145. Rosen EY, Johnson ML, Clifford SE, Somwar R, Kherani JF, Son J et al (2021) Overcoming MET-dependent resistance to selective RET inhibition in patients with RET fusion-positive lung cancer by combining selpercatinib with crizotinib. Clin Cancer Res Off J Am Assoc Cancer Res 27(1):34–42

    Article  CAS  Google Scholar 

  146. Abe H, Kamai T (2013) Recent advances in the treatment of metastatic renal cell carcinoma. Int J Urol Off J Jpn Urol Assoc 20(10):944–955

    CAS  Google Scholar 

  147. Yesilkanal AE, Johnson GL, Ramos AF, Rosner MR (2021) New strategies for targeting kinase networks in cancer. J Biol Chem 297(4):101128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Sinha D, Moseley P, Lu X, Wright Q, Gabrielli B, Frazer IH et al (2022) Repurposing of commercially existing molecular target therapies to boost the clinical efficacy of immune checkpoint blockade. Cancers 14(24):6150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Pottier C, Fresnais M, Gilon M, Jérusalem G, Longuespée R, Sounni NE (2020) Tyrosine kinase inhibitors in cancer: breakthrough and challenges of targeted therapy. Cancers 12(3):731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Jones D, Bopaiah J, Alghamedy F, Jacobs N, Weiss HL, de Jong WA et al (2018) Polypharmacology within the full kinome: a machine learning approach. AMIA Jt Summits Transl Sci Proc 2017:98–107

    PubMed  Google Scholar 

  151. Zhavoronkov A, Ivanenkov YA, Aliper A, Veselov MS, Aladinskiy VA, Aladinskaya AV et al (2019) Deep learning enables rapid identification of potent DDR1 kinase inhibitors. Nat Biotechnol 37(9):1038–1040

    Article  CAS  PubMed  Google Scholar 

  152. Desai B, Dixon K, Farrant E, Feng Q, Gibson KR, van Hoorn WP et al (2013) Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform. J Med Chem 56(7):3033–3047

    Article  CAS  PubMed  Google Scholar 

  153. Benz M, Molla MR, Böser A, Rosenfeld A, Levkin PA (2019) Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening. Nat Commun 10(1):2879

    Article  PubMed  PubMed Central  Google Scholar 

  154. Sontheimer-Phelps A, Hassell BA, Ingber DE (2019) Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer 19(2):65–81

    Article  CAS  PubMed  Google Scholar 

  155. Linifanib (2010) Drugs in R&D. 10(2):111–122

  156. Adachi Y, Matsuki M, Watanabe H, Takase K, Kodama K, Matsui J et al (2019) Antitumor and antiangiogenic activities of lenvatinib in mouse xenograft models of vascular endothelial growth factor-induced hypervascular human hepatocellular carcinoma. Cancer Invest 37(4–5):185–198

    Article  CAS  PubMed  Google Scholar 

  157. Méndez-Vidal MJ, Molina Á, Anido U, Chirivella I, Etxaniz O, Fernández-Parra E et al (2018) Pazopanib: evidence review and clinical practice in the management of advanced renal cell carcinoma. BMC Pharmacol Toxicol 19(1):77

    Article  PubMed  PubMed Central  Google Scholar 

  158. Hutson T, Davis I, Machiels J, De Souza P, Baker K, Bordogna W et al (2008) Biomarker analysis and final efficacy and safety results of a phase II renal cell carcinoma trial with pazopanib (GW786034), a multi-kinase angiogenesis inhibitor. J Clin Oncol 26(15 suppl):5046

    Article  Google Scholar 

  159. Adelaiye-Ogala R, Damayanti NP, Orillion AR, Arisa S, Chintala S, Titus MA et al (2018) Therapeutic targeting of sunitinib-induced AR phosphorylation in renal cell carcinoma. Can Res 78(11):2886–2896

    Article  CAS  Google Scholar 

  160. Abbas MN, Tan WS, Kichenadasse G (2021) Sorafenib-related generalized eruptive keratoacanthomas (Grzybowski syndrome): a case report. J Med Case Rep 15(1):481

    Article  PubMed  PubMed Central  Google Scholar 

  161. Abdelgalil AA, Alkahtani HM, Al-Jenoobi FI (2019) Sorafenib. Profiles of drug substances, excipients, and related methodology, vol 44. Elsevier, Amsterdam, pp 239–266

    Chapter  Google Scholar 

  162. Durham BH, Lopez Rodrigo E, Picarsic J, Abramson D, Rotemberg V, De Munck S et al (2019) Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms. Nat Med 25(12):1839–1842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Tap WD, Singh AS, Anthony SP, Sterba M, Zhang C, Healey JH et al (2022) Results from phase I extension study assessing pexidartinib treatment in six cohorts with solid tumors including TGCT, and abnormal CSF1 transcripts in TGCT. Clin Cancer Res Off J Am Assoc Cancer Res 28(2):298–307

    Article  CAS  Google Scholar 

  164. Asgari A, Sharifzadeh S, Ghaderi A, Hosseini A, Ramezani A (2019) In vitro cytotoxic effect of trastuzumab in combination with Pertuzumab in breast cancer cells is improved by interleukin-2 activated NK cells. Mol Biol Rep 46(6):6205–6213

    Article  CAS  PubMed  Google Scholar 

  165. Feldinger K, Kong A (2015) Profile of neratinib and its potential in the treatment of breast cancer. Breast Cancer 7:147–162

    PubMed  PubMed Central  Google Scholar 

  166. Ogoshi Y, Shien K, Yoshioka T, Torigoe H, Sato H, Sakaguchi M et al (2019) Anti-tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations. Oncol Lett 17(3):2729–2736

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Subramaniam D, He AR, Hwang J, Deeken J, Pishvaian M, Hartley ML et al (2015) Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer. Curr Cancer Drug Targets 14(9):775–793

    Article  PubMed  Google Scholar 

  168. Zhang Y, Zhang J, Liu C, Du S, Feng L, Luan X et al (2016) Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells. Cancer Lett 382(2):176–185

    Article  CAS  PubMed  Google Scholar 

  169. Abdullah MN, Ali Y, Abd HS (2021) Insights into the structure and drug design of benzimidazole derivatives targeting the epidermal growth factor receptor (EGFR). Chem Biol Drug Des 100(6):921–934

    Article  PubMed  Google Scholar 

  170. Abdel-Mohsen HT, Abdullaziz MA, Kerdawy AME, Ragab FAF, Flanagan KJ, Mahmoud AEE et al (2020) Targeting receptor tyrosine kinase VEGFR-2 in hepatocellular cancer: rational design, synthesis and biological evaluation of 1,2-disubstituted benzimidazoles. Molecules (Basel, Switzerland). 25(4):770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Bauer S, George S, von Mehren M, Heinrich MC (2021) Early and next-generation KIT/PDGFRA kinase inhibitors and the future of treatment for advanced gastrointestinal stromal tumor. Front Oncol 11:672500

    Article  PubMed  PubMed Central  Google Scholar 

  172. Yoshikawa S, Hara T, Suzuki M, Fujioka M, Taniguchi Y, Hirata KI (2020) Imatinib dramatically improved pulmonary hypertension caused by pulmonary tumor thrombotic microangiopathy (PTTM) associated with metastatic breast cancer. Int Heart J 61(3):624–628

    Article  PubMed  Google Scholar 

  173. Guan M, Tong Y, Guan M, Liu X, Wang M, Niu R et al (2018) Lapatinib inhibits breast cancer cell proliferation by influencing PKM2 expression. Technol Cancer Res Treat 17:1533034617749418

    Article  PubMed  PubMed Central  Google Scholar 

  174. Wu Z, Gabrielson A, Hwang JJ, Pishvaian MJ, Weiner LM, Zhuang T et al (2015) Phase II study of lapatinib and capecitabine in second-line treatment for metastatic pancreatic cancer. Cancer Chemother Pharmacol 76(6):1309–1314

    Article  CAS  PubMed  Google Scholar 

  175. Kjær I, Lindsted T, Fröhlich C, Olsen JV, Horak ID, Kragh M et al (2016) Cetuximab resistance in squamous carcinomas of the upper aerodigestive tract is driven by receptor tyrosine kinase plasticity: potential for mAb mixtures. Mol Cancer Ther 15(7):1614–1626

    Article  PubMed  Google Scholar 

  176. Goulet DR, Chatterjee S, Lee WP, Waight AB, Zhu Y, Mak AN (2022) Engineering an enhanced EGFR engager: humanization of cetuximab for improved developability. Antibodies (Basel, Switzerland) 11(1):6

    CAS  PubMed  Google Scholar 

  177. Padda IS, Parmar M (2022) Lenvatinib. StatPearls. StatPearls Publishing, Treasure Island (FL)

    Google Scholar 

  178. Albiges L, Barthélémy P, Gross-Goupil M, Negrier S, Needle MN, Escudier B (2021) TiNivo: safety and efficacy of tivozanib-nivolumab combination therapy in patients with metastatic renal cell carcinoma. Ann Oncol Off J Eur Soc Med Oncol 32(1):97–102

    Article  CAS  Google Scholar 

  179. Alqahtani T, Alswied A, Sun D (2021) Selective antitumor activity of datelliptium toward medullary thyroid carcinoma by downregulating RET transcriptional activity. Cancers 13(13):3288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Gortany NK, Panahi G, Ghafari H, Shekari M, Ghazi-Khansari M (2021) Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition. Cancer Chemother Pharmacol 87(6):827–842

    Article  CAS  PubMed  Google Scholar 

  181. Sohn SH, Kim B, Sul HJ, Choi BY, Kim HS, Zang DY (2020) Foretinib inhibits cancer stemness and gastric cancer cell proliferation by decreasing CD44 and c-MET signaling. Onco Targets Ther 13:1027–1035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Jiang S, Jiang T, Huang H, Chen X, Li L, Wang Z et al (2022) CHMFL-BMX-078, a BMX inhibitor, overcomes the resistance of melanoma to vemurafenib via inhibiting AKT pathway. Chem Biol Interact 351:109747

    Article  CAS  PubMed  Google Scholar 

  183. Yu W, Ye F, Yuan X, Ma Y, Mao C, Li X et al (2021) A phase I/II clinical trial on the efficacy and safety of NKT cells combined with gefitinib for advanced EGFR-mutated non-small-cell lung cancer. BMC Cancer 21(1):877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Yang JJ, Fang J, Shu YQ, Chang JH, Chen GY, He JX et al (2021) A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients with EGFR-mutated, MET-amplified advanced non-small-cell lung cancer. Invest New Drugs 39(2):477–487

    Article  CAS  PubMed  Google Scholar 

  185. Li T, Qian Y, Zhang C, Uchino J, Provencio M, Wang Y et al (2021) Anlotinib combined with gefitinib can significantly improve the proliferation of epidermal growth factor receptor-mutant advanced non-small cell lung cancer in vitro and in vivo. Transl Lung Cancer Res 10(4):1873–1888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Agarwal N, Azad A, Carles J, Chowdhury S, McGregor B, Merseburger AS et al (2022) A Phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer. Future Oncol (Lond, Engl). 18(10):1185–1198

    Article  CAS  Google Scholar 

  187. Tian M, Chen XS, Li LY, Wu HZ, Zeng D, Wang XL et al (2021) Inhibition of AXL enhances chemosensitivity of human ovarian cancer cells to cisplatin via decreasing glycolysis. Acta Pharmacol Sin 42(7):1180–1189

    Article  CAS  PubMed  Google Scholar 

  188. Suzuki S, Yamamoto M, Sanomachi T, Togashi K, Seino S, Sugai A et al (2021) Lurasidone sensitizes cancer cells to osimertinib by inducing autophagy and reduction of survivin. Anticancer Res 41(9):4321–4331

    Article  CAS  PubMed  Google Scholar 

  189. Zhou W, Gao Y, Tong Y, Wu Q, Zhou Y, Li Y (2021) Anlotinib enhances the antitumor activity of radiofrequency ablation on lung squamous cell carcinoma. Pharmacol Res 164:105392

    Article  CAS  PubMed  Google Scholar 

  190. Nakagawa N, Miyake N, Ochi N, Yamane H, Takeyama M, Nagasaki Y et al (2021) Targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer cells. Exp Cell Res 409(2):112940

    Article  CAS  PubMed  Google Scholar 

  191. Kudo M, Motomura K, Wada Y, Inaba Y, Sakamoto Y, Kurosaki M et al (2021) Avelumab in combination with axitinib as first-line treatment in patients with advanced hepatocellular carcinoma: results from the phase 1b VEGF liver 100 trial. Liver Cancer 10(3):249–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Zhu W, Wu J, Cui M, Zhang L (2020) Durable clinical benefit from pyrotinib combined with carboplatin in HER2-positive relapsed breast cancer previously treated with taxanes, anthracyclines, and trastuzumab. Ann Palliat Med 9(5):3684–3689

    Article  PubMed  Google Scholar 

  193. Nishiyama A, Yamada T, Kita K, Wang R, Arai S, Fukuda K et al (2018) Foretinib overcomes entrectinib resistance associated with the NTRK1 G667C mutation in NTRK1 fusion-positive tumor cells in a brain metastasis model. Clin Cancer Res Off J Am Assoc Cancer Res 24(10):2357–2369

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank all of those whose fruitful research has contributed in any way to the elucidation of the role of receptor tyrosine kinases in cancer pathogenesis and receptor tyrosine kinase inhibitors in cancer therapy.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article. MRH was supported by US NIH Grants R01AI050875 and R21AI121700.

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Author notes

  1. Nasim Ebrahimi and Elmira Fardi shared co-first authorship.

Authors and Affiliations

  1. Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran

    Nasim Ebrahimi

  2. Medical Branch, Islamic Azad University of Tehran, Tehran, Iran

    Elmira Fardi

  3. Laboratory of Regenerative and Medical Innovation, Pasteur Institute of Iran, Tehran, Iran

    Hajarossadat Ghaderi

  4. Division of Microbiology, Faculty of Basic Sciences, Islamic Azad University of Tehran East Branch, Tehran, Iran

    Sahar Palizdar

  5. Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz, Iran

    Roya Khorram

  6. Department of Orthopeadic Surgery, Kerman University of Medical Sciences, Kerman, Iran

    Reza Vafadar

  7. Master 1 Bio-Santé-Parcours Toulouse Graduate School of Cancer, Ageing and Rejuvenation (CARe), Université Toulouse III-Paul Sabatier, Toulouse, France

    Masoud Ghanaatian

  8. Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran

    Fatemeh Rezaei-Tazangi

  9. Department of Molecular and Cell Biology, Faculty of Basic Science, Uinversity of Mazandaran, Babolsar, Iran

    Payam Baziyar

  10. Department of Biological Science and Technology, Faculty of Nano and Bio Science and Technology, Persian Gulf University, Bushehr, 75169, Iran

    Amirhossein Ahmadi

  11. Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa

    Michael R. Hamblin

  12. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA

    Amir Reza Aref

  13. Translational Medicine Group, Xsphera Biosciences, 6 Tide Street, Boston, MA, 02210, USA

    Amir Reza Aref

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  1. Nasim Ebrahimi
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Contributions

NE, and EF designed the review paper and wrote the manuscript, HG, SP, RK, RV, MG, RFT, and, PB contributed to writing and editing the manuscript, AHA, MRH and ARA reviewed and revised the final version of manuscript and supervised the study.

Corresponding authors

Correspondence to Amirhossein Ahmadi, Michael R. Hamblin or Amir Reza Aref.

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Conflict of interest

MRH declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc, Cleveland, OH; Hologenix Inc. Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc, Minneapolis-St. Paul MN; Sunlighten, Kansas City, MO; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany; Klox Asia, Guangzhou, China. Stockholding: Niraxx Light Therapeutics, Inc, Irvine CA; JelikaLite Corp, New York NY. The other authors declare that they have no competing interests.

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Ebrahimi, N., Fardi, E., Ghaderi, H. et al. Receptor tyrosine kinase inhibitors in cancer. Cell. Mol. Life Sci. 80, 104 (2023). https://doi.org/10.1007/s00018-023-04729-4

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