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Effect of Tyrosine Kinase Inhibitors on Wound Healing and Tissue Repair: Implications for Surgery in Cancer Patients

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Abstract

Small-molecule tyrosine kinase inhibitors (TKIs) represent a major advance in the treatment of certain forms of cancer. Unexpectedly, however, their use is associated with serious toxic effects on many vital organs and functions. Some of these effects, such as venous thromboembolism, haemorrhage, gastric perforation and a potential for impaired tissue healing, have direct implications for the safety of surgery in cancer patients. A number of currently approved TKIs are suspected or have been reported to impair wound healing but, understandably, there have been no formal pre- or post-approval clinical trials to evaluate the extent of the risk. Consequently, drug labels typically recommend discontinuation of the TKI concerned prior to elective surgery. In patients with gastric perforation, permanent discontinuation is advised. These recommendations, which are based on a precautionary principle, raise a dilemma, especially in patients with TKI-responsive tumours. This review focuses on the labelled potential of these novel antineoplastic agents to impair tissue repair and wound healing, and the evidence concerning the likely mechanisms involved. At present, because of the lack of formal clinical data, there are no evidence-based guidelines on the management of surgery in patients treated with TKIs. There is a need for a central registry of clinical outcomes following emergency surgery in cancer patients receiving TKIs and TKI-naïve matched controls. Analysis of outcomes data from such registries will assist in formulating guidelines on the management of elective surgery in TKI-treated patients. If TKIs are shown to significantly impair wound healing, patients receiving TKI therapy will require special monitoring and a collaborative approach between oncologists and surgeons for individualized reappraisal of the risk/benefit of the TKI treatment.

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References

  1. Shah RR, Roberts SA, Shah DR. A fresh perspective on comparing the FDA and the CHMP/EMA: approval of antineoplastic tyrosine kinase inhibitors. Br J Clin Pharmacol. 2013;76:396–411.

    Article  CAS  PubMed  Google Scholar 

  2. Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf. 2013;36:491–503.

    Article  CAS  PubMed  Google Scholar 

  3. Shah DR, Shah RR, Morganroth J. Tyrosine kinase inhibitors: their on-target toxicities as potential indicators of efficacy. Drug Saf. 2013;36:413–26.

    Article  CAS  PubMed  Google Scholar 

  4. Shah RR, Morganroth J, Shah DR. Cardiovascular safety of tyrosine kinase inhibitors: with a special focus on cardiac repolarization (QT interval). Drug Saf. 2013;36:295–316.

    Article  CAS  PubMed  Google Scholar 

  5. Johnson JR, Ning Y-M, Farrell A, et al. Accelerated approval of oncology products: the Food and Drug Administration experience. J Natl Cancer Inst. 2011;103:636–44.

    Article  PubMed  Google Scholar 

  6. Seruga B, Sterling L, Wang L, et al. Reporting of serious adverse drug reactions of targeted anticancer agents in pivotal phase III clinical trials. J Clin Oncol. 2011;29:174–85.

    Article  CAS  PubMed  Google Scholar 

  7. Niraula S, Seruga B, Ocana A, et al. The price we pay for progress: a meta-analysis of harms of newly approved anticancer drugs. J Clin Oncol. 2012;30:3012–9.

    Article  PubMed  Google Scholar 

  8. Jonsson B, Bergh J. Hurdles in anticancer drug development from a regulatory perspective. Nat Rev Clin Oncol. 2012;9:236–43.

    Article  CAS  PubMed  Google Scholar 

  9. Broglio KR, Berry DA. Detecting an overall survival benefit that is derived from progression-free survival. J Natl Cancer Inst. 2009;101:1642–9.

    Article  PubMed  Google Scholar 

  10. Sherrill B, Kaye JA, Sandin R, et al. Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology. Onco Targets Ther. 2012;5:287–96.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Food and Drug Administration. FDA drug safety communication (5 November 2013): FDA asks manufacturer of the leukemia drug Iclusig (ponatinib) to suspend marketing and sales. http://www.fda.gov/drugs/drugsafety/ucm373040.htm. Accessed 9 Nov 2013.

  12. Food and Drug Administration. Gilotrif (afatinib) label approved on 12 July 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201292s000lbl.pdf. Accessed 10 Sep 2013.

  13. Food and Drug Administration. Inlyta (axitinib) label approved on 27 January 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202324lbl.pdf. Accessed 10 Sep 2013.

  14. Food and Drug Administration. Bosulif (bosutinib) label approved on 4 September 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf. Accessed 10 Sep 2013.

  15. Food and Drug Administration. Cometriq (cabozantinib) label approved on 29 November 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203756lbl.pdf. Accessed 10 Sep 2013.

  16. Food and Drug Administration. Xalkori (crizotinib) label approved on 24 February 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202570s003lbl.pdf. Accessed 10 Sep 2013.

  17. Food and Drug Administration. Tafinlar (dabrafenib) label approved on 29 May 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202806s000lbl.pdf. Accessed 10 Sep 2013.

  18. Food and Drug Administration. Sprycel (dasatinib) label approved on 7 October 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021986s009s010lbl.pdf. Accessed 10 Sep 2013.

  19. Food and Drug Administration. Tarceva (erlotinib) label approved on 17 April 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021743s017lbl.pdf. Accessed 10 Sep 2013.

  20. Food and Drug Administration. Iressa (gefitinib) label approved on 17 June 2005. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021399s008lbl.pdf. Accessed 10 Sep 2013.

  21. Food and Drug Administration. Imbruvica (ibrutinib) label approved on 13 November 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/205552s000lbl.pdf. Accessed 18 Nov 2013.

  22. Food and Drug Administration. Gleevec (imatinib) label approved on 31 January 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021588s035lbl.pdf. Accessed 10 Sep 2013.

  23. Food and Drug Administration. Tykerb (lapatinib) label approved on 14 February 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022059s013lbl.pdf. Accessed 10 Sep 2013.

  24. Food and Drug Administration. Tasigna (nilotinib) label approved on 1 May 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022068s012lbl.pdf. Accessed 10 Sep 2013.

  25. Food and Drug Administration. Votrient (pazopanib) label approved on 15 November 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s013lbl.pdf. Accessed 10 Sep 2013.

  26. Food and Drug Administration. Iclusig (ponatinib) label approved on 14 December 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203469lbl.pdf. Accessed 10 Sep 2013.

  27. Food and Drug Administration. Stivarga (regorafenib) label approved on 27 September 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203085lbl.pdf. Accessed 10 Sep 2013.

  28. Food and Drug Administration. Jakafi (ruxolitinib) label approved on 21 June 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202192s001lbl.pdf. Accessed 10 Sep 2013.

  29. Food and Drug Administration. Nexavar (sorafenib) label approved on 14 October 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021923s012lbl.pdf. Accessed 10 Sep 2013.

  30. Food and Drug Administration. Sutent (sunitinib) label approved on 16 November 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021938s021s022s023lbl.pdf. Accessed 10 Sep 2013.

  31. Food and Drug Administration. Mekinist (trametinib) label approved on 29 May 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf. Accessed 10 Sep 2013.

  32. Food and Drug Administration. Caprelsa (vandetanib) label approved on 9 October 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022405s003lbl.pdf. Accessed 10 Sep 2013.

  33. Food and Drug Administration. Zelboraf (vemurafenib) label approved on 17 August 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429s000lbl.pdf. Accessed 10 Sep 2013.

  34. Elice F, Rodeghiero F, Falanga A, et al. Thrombosis associated with angiogenesis inhibitors. Best Pract Res Clin Haematol. 2009;22:115–28.

    Article  CAS  PubMed  Google Scholar 

  35. Food and Drug Administration. Avastin (bevacizumab) label approved on 26 January 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125085s267lbl.pdf. Accessed 10 Sep 2013.

  36. Borzomati D, Nappo G, Valeri S, et al. Infusion of bevacizumab increases the risk of intestinal perforation: results on a series of 143 patients consecutively treated. Updates Surg. 2013;65:121–4.

    Article  PubMed  Google Scholar 

  37. Fakih MG, Lombardo JC. Bevacizumab-induced nasal septum perforation. Oncologist. 2006;11:85–6.

    Article  PubMed  Google Scholar 

  38. Traina TA, Norton L, Drucker K, et al. Nasal septum perforation in a bevacizumab-treated patient with metastatic breast cancer. Oncologist. 2006;11:1070–1.

    Article  PubMed  Google Scholar 

  39. Food and Drug Administration. Erbitux (cetuximab) label approved on 4 March 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125084s242lbl.pdf. Accessed 10 Sep 2013.

  40. Food and Drug Administration. Vectibix (panitumumab) label approved on 28 March 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125147s169lbl.pdf. Accessed 10 Sep 2013.

  41. Fuloria J. Safety profiles of current antiangiogenic therapies for metastatic colorectal cancer. Onco Targets Ther. 2012;5:133–42.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Kim TI, Chung JL, Hong JP, et al. Bevacizumab application delays epithelial healing in rabbit cornea. Invest Ophthalmol Vis Sci. 2009;50:4653–9.

    Article  PubMed  Google Scholar 

  43. Kim EC, Lee WS, Kim MS. The inhibitory effects of bevacizumab eye drops on NGF expression and corneal wound healing in rats. Invest Ophthalmol Vis Sci. 2010;51:4569–73.

    Article  PubMed  Google Scholar 

  44. Scappaticci FA, Fehrenbacher L, Cartwright T, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91:173–80.

    Article  CAS  PubMed  Google Scholar 

  45. D’Angelica M, Kornprat P, Gonen M, et al. Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study. Ann Surg Oncol. 2007;14:759–65.

    Article  PubMed  Google Scholar 

  46. Kesmodel SB, Ellis LM, Lin E, et al. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008;26:5254–60.

    Article  PubMed  Google Scholar 

  47. Mahfud M, Breitenstein S, El-Badry AM, et al. Impact of preoperative bevacizumab on complications after resection of colorectal liver metastases: case-matched control study. World J Surg. 2010;34:92–100.

    Article  PubMed  Google Scholar 

  48. Tamandl D, Gruenberger B, Klinger M, et al. Liver resection remains a safe procedure after neoadjuvant chemotherapy including bevacizumab: a case-controlled study. Ann Surg. 2010;252:124–30.

    Article  PubMed  Google Scholar 

  49. Constantinidou A, Cunningham D, Shurmahi F, et al. Perioperative chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer undergoing liver resection. Clin Colorectal Cancer. 2013;12:15–22.

    Article  CAS  PubMed  Google Scholar 

  50. Dede K, Mersich T, Besznyák I, et al. Bevacizumab treatment before resection of colorectal liver metastases: safety, recovery of liver function, pathologic assessment. Pathol Oncol Res. 2013;19:501–8.

    Article  CAS  PubMed  Google Scholar 

  51. Lubezky N, Winograd E, Papoulas M, et al. Perioperative complications after neoadjuvant chemotherapy with and without bevacizumab for colorectal liver metastases. J Gastrointest Surg. 2013;17:527–32.

    Article  PubMed  Google Scholar 

  52. Li DB, Ye F, Wu XR, et al. Preoperative administration of bevacizumab is safe for patients with colorectal liver metastases. World J Gastroenterol. 2013;19:761–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Reddy SK, Morse MA, Hurwitz HI, et al. Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg. 2008;206:96–106.

    Article  PubMed  Google Scholar 

  54. Clark AJ, Butowski NA, Chang SM, et al. Impact of bevacizumab chemotherapy on craniotomy wound healing. J Neurosurg. 2011;114:1609–16.

    Article  PubMed  Google Scholar 

  55. Roman CD, Choy H, Nanney L, et al. Vascular endothelial growth factor-mediated angiogenesis inhibition and postoperative wound healing in rats. J Surg Res. 2002;105:43–7.

    Article  CAS  PubMed  Google Scholar 

  56. Kaftan H, Reuther L, Miehe B, et al. Delay of tympanic membrane wound healing in rats with topical application of a tyrosine kinase inhibitor. Wound Repair Regen. 2008;16:364–9.

    Article  PubMed  Google Scholar 

  57. Kaftan H, Reuther L, Miehe B, et al. The influence of inhibition of the epidermal growth factor receptor on tympanic membrane wound healing in rats. Growth Factors. 2010;28:286–92.

    Article  CAS  PubMed  Google Scholar 

  58. Lee SM, Buchler T, Joseph T, et al. Bilateral eardrum perforation after long-term treatment with erlotinib. J Clin Oncol. 2008;26:2582–4.

    Article  CAS  PubMed  Google Scholar 

  59. Kaftan H, Reuther L, Miehe B, et al. Inhibition of fibroblast growth factor receptor 1: influence on tympanic membrane wound healing in rats. Eur Arch Otorhinolaryngol. 2012;269:87–92.

    Article  PubMed  Google Scholar 

  60. Food and Drug Administration. Product reviews and labels. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed 10 Sep 2013.

  61. European Medicines Agency. European public assessment reports: assessment history and product information. http://www.emea.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d124. Accessed 10 Sep 2013.

  62. European Medicines Agency. European public assessment report for Sutent (sunitinib) (10 January 2007). http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000687/WC500057733.pdf. Accessed 10 Sep 2013.

  63. Ko J, Ross J, Awad H, et al. The effects of ZD6474, an inhibitor of VEGF signaling, on cutaneous wound healing in mice. J Surg Res. 2005;129:251–9.

    Article  CAS  PubMed  Google Scholar 

  64. Johannsen M, Florcken A, Bex A, et al. Can tyrosine kinase inhibitors be discontinued in patients with metastatic renal cell carcinoma and a complete response to treatment? A multicentre, retrospective analysis. Eur Urol. 2009;55:1430–9.

    Article  CAS  PubMed  Google Scholar 

  65. Johannsen M, Staehler M, Ohlmann CH, et al. Outcome of treatment discontinuation in patients with metastatic renal cell carcinoma and no evidence of disease following targeted therapy with or without metastasectomy. Ann Oncol. 2011;22:657–63.

    Article  CAS  PubMed  Google Scholar 

  66. Harshman LC, Yu RJ, Allen GI, et al. Surgical outcomes and complications associated with presurgical tyrosine kinase inhibition for advanced renal cell carcinoma (RCC). Urol Oncol. 2013;31:379–85.

    Article  CAS  PubMed  Google Scholar 

  67. Govindan R, Behnken D, Read W, et al. Wound healing is not impaired by the epidermal growth factor receptor-tyrosine kinase inhibitor gefitinib. Ann Oncol. 2003;14:1330–1.

    Article  CAS  PubMed  Google Scholar 

  68. Johnson KS, Levin F, Chu DS. Persistent corneal epithelial defect associated with erlotinib treatment. Cornea. 2009;28:706–7.

    Article  PubMed  Google Scholar 

  69. Ibrahim E, Dean WH, Price N, et al. Perforating corneal ulceration in a patient with lung metastatic adenocarcinoma treated with gefitinib: a case report. Case Rep Ophthalmol Med. 2012;2012:379132.

    PubMed Central  PubMed  Google Scholar 

  70. Yano S, Kondo K, Yamaguchi M, et al. Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition. Anticancer Res. 2003;23(5A):3639–50.

    CAS  PubMed  Google Scholar 

  71. Saint-Jean A, Sainz de la Maza M, Morral M, et al. Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases. Ophthalmology. 2012;119:1798–802.

    Article  PubMed  Google Scholar 

  72. Food and Drug Administration. Regranex (becaplermin) label approved on 11 March 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103691s5095lbl.pdf. Accessed 10 Sep 2013.

  73. Yu CQ, Zhang M, Matis KI, et al. Vascular endothelial growth factor mediates corneal nerve repair. Invest Ophthalmol Vis Sci. 2008;49:3870–8.

    Article  PubMed Central  PubMed  Google Scholar 

  74. Muller AK, Meyer M, Werner S. The roles of receptor tyrosine kinases and their ligands in the wound repair process. Semin Cell Dev Biol. 2012;23:963–70.

    Article  PubMed  Google Scholar 

  75. Bao P, Kodra A, Tomic-Canic M, et al. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009;153:347–58.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Somanath PR, Chen J, Byzova TV. Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing. Angiogenesis. 2008;11:277–88.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Perrotte P, Matsumoto T, Inoue K, et al. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res. 1999;5:257–65.

    CAS  PubMed  Google Scholar 

  78. Pastor JC, Calonge M. Epidermal growth factor and corneal wound healing: a multicenter study. Cornea. 1992;11:311–4.

    Article  CAS  PubMed  Google Scholar 

  79. Lou-Bonafonte JM, Bonafonte-Marquez E, Bonafonte-Royo S, et al. Posology, efficacy, and safety of epidermal growth factor eye drops in 305 patients: logistic regression and group-wise odds of published data. J Ocul Pharmacol Ther. 2012;28:467–72.

    Article  CAS  PubMed  Google Scholar 

  80. Schneider MR, Werner S, Paus R, et al. Beyond wavy hairs: the epidermal growth factor receptor and its ligands in skin biology and pathology. Am J Pathol. 2008;173:14–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Yu FX, Yin J, Xu K, et al. Growth factors and corneal epithelial wound healing. Brain Res Bull. 2010;81:229–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Márquez EB, De Ortueta D, Royo SB, et al. Epidermal growth factor receptor in corneal damage: update and new insights from recent reports. Cutan Ocul Toxicol. 2011;30:7–14.

    Article  PubMed  Google Scholar 

  83. Majumdar AP, Edgerton EA, Arlow FL. Gastric mucosal tyrosine kinase activity during aging and its relationship to cell proliferation in rats. Biochim Biophys Acta. 1988;965:97–105.

    Article  CAS  PubMed  Google Scholar 

  84. Lin W, Kao HW, Robinson D, et al. Tyrosine kinases and gastric cancer. Oncogene. 2000;19:5680–9.

    Article  CAS  PubMed  Google Scholar 

  85. Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci. 2005;50(Suppl 1):S24–33.

    Article  CAS  PubMed  Google Scholar 

  86. Tarnawski AS, Ahluwalia A. Molecular mechanisms of epithelial regeneration and neovascularization during healing of gastric and esophageal ulcers. Curr Med Chem. 2012;19:16–27.

    Article  CAS  PubMed  Google Scholar 

  87. Pai R, Szabo IL, Giap AQ, et al. Nonsteroidal anti-inflammatory drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK and tensin signaling. Life Sci. 2001;69:3055–71.

    Article  CAS  PubMed  Google Scholar 

  88. Choi GH, Park HS, Kim KR, et al. Increased expression of epidermal growth factor receptor and betacellulin during the early stage of gastric ulcer healing. Mol Med Rep. 2008;1:505–10.

    CAS  PubMed  Google Scholar 

  89. Elitsur Y, Majumdar AP, Tureaud J, et al. Tryosine kinase and ornithine decarboxylase activation in children with Helicobacter pylori gastritis. Life Sci. 1999;65:1373–80.

    Article  CAS  PubMed  Google Scholar 

  90. Meyer-ter-Vehn T, Covacci A, Kist M, et al. Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun. J Biol Chem. 2000;275:16064–72.

    Article  CAS  PubMed  Google Scholar 

  91. Wong BC, Wang WP, So WH, et al. Epidermal growth factor and its receptor in chronic active gastritis and gastroduodenal ulcer before and after Helicobacter pylori eradication. Aliment Pharmacol Ther. 2001;15:1459–65.

    Article  CAS  PubMed  Google Scholar 

  92. Coyle WJ, Sedlack RE, Nemec R, et al. Eradication of Helicobacter pylori normalizes elevated mucosal levels of epidermal growth factor and its receptor. Am J Gastroenterol. 1999;94:2885–9.

    Article  CAS  PubMed  Google Scholar 

  93. Duan WR, Patyna S, Kuhlmann MA, et al. A multitargeted receptor tyrosine kinase inhibitor, SU6668, does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice. J Invest Surg. 2006;19:245–54.

    Article  PubMed  Google Scholar 

  94. Schäfer M, Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol. 2008;9:628–38.

    Article  PubMed  Google Scholar 

  95. Ceelen W, Pattyn P, Mareel M. Surgery, wound healing, and metastasis: recent insights and clinical implications. Crit Rev Oncol Haematol. 2014;89:16–26.

    Article  Google Scholar 

  96. Chmielowiec J, Borowiak M, Morkel M, et al. c-Met is essential for wound healing in the skin. J Cell Biol. 2007;177:151–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Luo JC, Lin HY, Lu CL, et al. Growth factors expression in patients with erosive esophagitis. Transl Res. 2008;152:81–7.

    Article  CAS  PubMed  Google Scholar 

  98. Meyer M, Muller AK, Yang J, et al. FGF receptors 1 and 2 are key regulators of keratinocyte migration in vitro and in wounded skin. J Cell Sci. 2012;125(Pt 23):5690–701.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Demidova-Rice TN, Wolf L, Deckenback J, et al. Human platelet-rich plasma- and extracellular matrix-derived peptides promote impaired cutaneous wound healing in vivo. PLoS ONE. 2012;7(2):e32146.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003;83:835–70.

    CAS  PubMed  Google Scholar 

  101. Cazander G, Jukema GN, Nibbering PH. Complement activation and inhibition in wound healing. Clin Dev Immunol. 2012;2012:Article ID 534291.

  102. Miyamoto K, Kobayashi T, Hayashi Y, et al. Involvement of stem cell factor and c-kit in corneal wound healing in mice. Mol Vision. 2012;18:1505–15.

    CAS  Google Scholar 

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Conflicts of Interest

No sources of funding were used in the preparation of this review. Devron Shah and Shamik Dholakia are doctors under training at district general hospitals and have no consultancy relationships. Rashmi Shah provides expert consultancy services on the development and safety of new drugs to a number of pharmaceutical companies. Devron Shah, Shamik Dholakia and Rashmi Shah have no other conflicts of interest that are directly relevant to the content of this review.

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  1. Royal Berkshire Hospital, Reading, UK

    Devron R. Shah

  2. University Hospital of Wales, Heath Park, Cardiff, UK

    Shamik Dholakia

  3. Rashmi Shah Consultancy Ltd, 8 Birchdale, Gerrards Cross, Buckinghamshire, SL9  7JA, UK

    Rashmi R. Shah

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Shah, D.R., Dholakia, S. & Shah, R.R. Effect of Tyrosine Kinase Inhibitors on Wound Healing and Tissue Repair: Implications for Surgery in Cancer Patients. Drug Saf 37, 135–149 (2014). https://doi.org/10.1007/s40264-014-0139-x

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