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Mechanisms of cutaneous toxicities to EGFR inhibitors

Nature Reviews Cancer volume 6, pages 803–812 (2006)Cite this article

Key Points

  • Cutaneous toxicities that result from treatment with epidermal growth factor receptor inhibitors are common, affecting 45–100% of patients.

  • The most frequent reactions are: a papulopustular rash that affects the face and upper trunk; dry and itchy skin; inflammation around the nails, with or without brittle or deformed nails; loss of hair on the scalp; and increased growth of the eyelashes and facial hair.

  • Although rarely life-threatening, these reactions cause significant physical and psycho-social discomfort, which might lead to a decreased quality of life and the modification or discontinuation of anticancer therapy.

  • There are currently no established guidelines to prevent or manage these reactions. Mechanism-based approaches have proved successful in the clinical setting, but controlled trials are lacking.

  • Projects that are directed towards understanding and treating this phenomenon are essential for the progress of targeted therapies against cancer.

Abstract

The increased target specificity of epidermal growth factor receptor (EGFR) inhibitors (EGFRIs) is associated with the reduction or abolition of nonspecific and haematopoietic side effects. However, coincident inhibition of receptor activity in tissues that depend on EGFR signalling for normal function has undesirable consequences. Because of the key role of EGFR signalling in skin, dermatological toxicities have frequently been described with EGFRIs. The resultant significant physical and psycho-social discomfort might lead to interruption or dose modification of anticancer agents. There is an urgent need for an improved understanding of these toxicities to develop adequate staging systems and mechanistically driven therapies, and to ensure quality of life and consistent antineoplastic therapy.

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Figure 1: Skin toxicities to EGFRIs (epidermal growth factor receptor inhibitors).
Figure 2: Structure of the skin and hair follicle.
Figure 3: The effects of EGFR inhibition in skin.
Figure 4: Model of EGFR-inhibitor-induced reactions.

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References

  1. Hynes, N. E. & Lane, H. A. ERBB receptors and cancer: the complexity of targeted inhibitors. Nature Rev. Cancer 5, 341–354 (2005).

    Article  CAS  Google Scholar 

  2. Dancey, J. & Sausville, E. A. Issues and progress with protein kinase inhibitors for cancer treatment. Nature Rev. Drug Discov. 2, 296–313 (2003).

    Article  CAS  Google Scholar 

  3. Molinari, E. et al. Cetuximab-induced acne. Dermatology. 211, 330–333 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Perez-Soler, R. & Saltz, L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J. Clin. Oncol. 23, 5235–5246 (2005). The relationship between cutaneous toxicity and clinical outcome has been shown in several studies, indicating that higher doses result in greater response. Therefore, an improved examination of rash during trials is encouraged.

    Article  PubMed  Google Scholar 

  5. Robert, C. et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 6, 491–500 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Jost, M., Kari, C. & Rodeck, U. The EGF receptor — an essential regulator of multiple epidermal functions. Eur. J. Dermatol. 10, 505–510 (2000).

    CAS  PubMed  Google Scholar 

  7. OSI Pharmaceuticals. Tarceva package insert (2005).

  8. ImClone Systems. Erbitux package insert (2006).

  9. Mendelsohn, J. & Baselga, J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J. Clin. Oncol. 21, 2787–2799 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Kari, C. et al. Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage. Cancer Res. 63, 1–5 (2003).

    CAS  PubMed  Google Scholar 

  11. Fuchs, E. & Raghavan S. Getting under the skin of epidermal morphogenesis. Nature Rev. Genet. 3, 199–209 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Candi, E., Schmidt, R. & Melino G. The cornified envelope: a model of cell death in the skin. Nature Rev. Mol. Cell Biol. 6, 328–340 (2005).

    Article  CAS  Google Scholar 

  13. Nanney, L. B., Stoscheck, C. M., King, L. E. Jr, Underwood, R. A. & Holbrook, K. A. Immunolocalization of epidermal growth factor receptors in normal developing human skin. J. Invest. Dermatol. 94, 742–748 (1990).

    Article  CAS  PubMed  Google Scholar 

  14. Miettinen, P. J. et al. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376, 337–341 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Murillas, R. et al. Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure. EMBO J. 14, 5216–5223 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pasonen-Seppanen. S. et al. EGF upregulates, whereas TGF-β downregulates, the hyaluronan synthases Has2 and Has3 in organotypic keratinocyte cultures: correlations with epidermal proliferation and differentiation. J. Invest. Dermatol. 120, 1038–1044 (2003).

    Article  PubMed  Google Scholar 

  17. Peus, D., Hamacher, L. & Pittelkow, MR. EGF-receptor tyrosine kinase inhibition induces keratinocyte growth arrest and terminal differentiation. J. Invest. Dermatol. 109, 751–756 (1997).

    Article  CAS  PubMed  Google Scholar 

  18. Kobayashi, T., Hashimoto, K., Okumura, H., Asada, H. & Yoshikawa K. Endogenous EGF-family growth factors are necessary for the progression from the G1 to S phase in human keratinocytes. J. Invest. Dermatol. 111, 616–620 (1998).

    Article  CAS  PubMed  Google Scholar 

  19. Stoll, S. W. et al. EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bcl-XL . Oncogene 16, 1493–1499 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Rodeck, U. et al. EGF-R-dependent regulation of keratinocyte survival. J. Cell Sci. 110, 113–121 (1997).

    Article  CAS  PubMed  Google Scholar 

  21. Woodworth, C. D. et al. Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment. Mol. Cancer Ther. 4, 650–658 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Mimeault, M., Bonenfant, D. & Batra, S. K. New advances on the functions of epidermal growth factor receptor and ceramides in skin cell differentiation, disorders and cancers. Skin Pharmacol. Physiol. 17, 153–166 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Sayama, K. et al. Apoptosis signal-regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation. J. Biol. Chem. 276, 999–1004 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Threadgill, D. W. et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 269, 230–234 (1995).

    Article  CAS  PubMed  Google Scholar 

  25. Hauser, P. J., Agrawal, D., Hackney, J. & Pledger. W. J. STAT3 activation accompanies keratinocyte differentiation. Cell. Growth Differ. 9, 847–855 (1998).

    CAS  PubMed  Google Scholar 

  26. Levy, D. E. & Darnell, J. E. Jr. Stats: transcriptional control and biological impact. Nature Rev. Mol. Cell Biol. 3, 651–662 (2002).

    Article  CAS  Google Scholar 

  27. Lorch, J. H. et al. Epidermal growth factor receptor inhibition promotes desmosome assembly and strengthens intercellular adhesion in squamous cell carcinoma cells. J. Biol. Chem. 279, 37191–37200 (2004).

    Article  CAS  PubMed  Google Scholar 

  28. Mascia, F., Mariani, V., Girolomoni, G. & Pastore, S. Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation. Am. J. Pathol. 163, 303–312 (2003). Inhibition of EGFR tyrosine kinase activity results in upregulation of chemokines that recruit monocytes and dendritic cells. Mice that have been treated with an EGFRI show a greater hypersensitivity response to a skin irritant.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pastore, S. et al. ERK1/2 regulates epidermal chemokine expression and skin inflammation. J. Immunol. 174, 5047–5056 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Vallbohmer, D. et al. Molecular determinants of cetuximab efficacy. J. Clin. Oncol. 23, 3536–3544 (2005).

    Article  PubMed  CAS  Google Scholar 

  31. Higgins, B. et al. Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models. Anticancer Drugs 15, 503–512 (2004). Nude mice that were treated with the low-molecular-weight EGFRI erlotinib developed skin lesions with scabs and inflammatory cells, implicating keratinocyte effects as an important event.

    Article  CAS  PubMed  Google Scholar 

  32. Gibson, T. B., Ranganatha, A. & Grothey, A. Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clin. Colorectal Cancer 6, 29–31 (2006).

    Article  PubMed  Google Scholar 

  33. Fisher, G. J. et al. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379, 335–339 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. El-Abaseri, T. B., Putta, S. & Hansen, L. A. Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. Carcinogenesis 27, 225–231 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Jost, M., Gasparro, F. P., Jensen, P. J. & Rodeck, U. Keratinocyte apoptosis induced by UVB radiation and CD95 ligation- differential protection through EGFR activation and Bcl-xL expression. J. Investig. Dermatol. 116, 860–866 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Jacot, W. et al. Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours. Br. J. Dermatol. 151, 238–241 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Sartor, C. I. Mechanisms of disease: radiosensitization by epidermal growth factor receptor inhibitors. Nature Clin. Pract. Oncol. 1, 80–87 (2004).

    Article  CAS  Google Scholar 

  38. Mitra, S. S. & Simcock, R. Erlotinib induced skin rash spares skin in previous radiotherapy field. J. Clin. Oncol. 24, e28–e29 (2006).

    Article  PubMed  Google Scholar 

  39. Hymes, S. R., Strom, E. & Fife, C. Radiation dermatitis: clinical presentation, pathophysiology, and treatment 2006. J. Am. Acad. Dermatol. 54, 28–46 (2006).

    Article  PubMed  Google Scholar 

  40. Yarden, Y. & Sliwkowski, M. X. Untangling the ErbB signalling network. Nature Rev. Mol. Cell Biol. 2, 127–137 (2001).

    Article  CAS  Google Scholar 

  41. Albanell, J. et al. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J. Clin. Oncol. 20, 110–124 (2002). Examination of skin in patients who were treated with an EGFRI showed morphological abnormalities, the expression of markers that indicate growth inhibition and altered differentiation.

    Article  CAS  PubMed  Google Scholar 

  42. Herbst, R. S. et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. J. Clin. Oncol. 20, 3815–3825 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Baselga, J. et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J. Clin. Oncol. 20, 4292–4302 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. Malik, S. N. Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients. Clin. Cancer Res. 9, 2478–2486 (2003).

    CAS  PubMed  Google Scholar 

  45. Tan, A. R., Yang, X. & Hewitt, S. M. Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. J. Clin. Oncol. 22, 3080–3090 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Busse, D. et a l. Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires upregulation of p27KIP1 independent of MAPK activity. J. Biol. Chem. 275, 6987–6995 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. Wakita, H. & Takigawa M. Activation of epidermal growth factor receptor promotes late terminal differentiation of cell–matrix interaction-disrupted keratinocytes. J. Biol. Chem. 274, 37285–37291 (1999).

    Article  CAS  PubMed  Google Scholar 

  48. Sano, S. et al. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nature Med. 11, 43–49 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Hofmeister, C. C. et al. Graft-versus-host disease of the skin: life and death on the epidermal edge. Biol. Blood Marrow Transplant. 10, 366–372 (2004).

    Article  PubMed  Google Scholar 

  50. Chave, T. A., Mortimer, N. J., Sladden, M. J., Hall, A. P. & Hutchinson, P. E. Toxic epidermal necrolysis: current evidence, practical management and future directions. Br. J. Dermatol. 153, 241–253 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Van Doorn, R., Kirtschig, G., Scheffer, E., Stoof, T. J. & Giaccone, G. Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor. Br. J. Dermatol. 147, 598–601 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Busam, K. J. et al. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br. J. Dermatol. 144, 1169–1176 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Pascual, J. C., Belinchon, I., Sivera, F. & Yuste, A. Severe cutaneous toxicity following treatment with gefitinib (ZD1839). Br. J. Dermatol. 153, 1222–1223 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Treudler, R. & Zouboulis, C. C. Follicular drug eruption induced by gefitinib (ZD 1839, iressa): clinical picture correlates with in vitro data of focal epidermal necrosis after epidermal growth factor inhibition in skin cultures. Int. J. Dermatol. 44, 167–168 (2005).

    Article  Google Scholar 

  55. Chang, G. C. et al. Complications of therapy in cancer patients: Case 1. Paronychia and skin hyperpigmentation induced by gefitinib in advanced non-small-cell lung cancer. J. Clin. Oncol. 22, 4646–4648 (2004).

    Article  PubMed  Google Scholar 

  56. Fernandez-Galar, M., Espana, A. & Lopez-Picazo, J. M. Acneiform lesions secondary to ZD1839, an inhibitor of the epidermal growth factor receptor. Clin. Exp. Dermatol. 29, 138–140 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Sergi, C., Kahl, P. & Otto, H. F. Immunohistochemical localization of transforming growth factor-α and epithelial growth factor receptor in human fetal developing skin, psoriasis and restrictive dermopathy. Pathol. Oncol. Res. 6, 250–255 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Tavakkol, A., Varani, J., Elder, J. T. & Zouboulis, C. C. Maintenance of human skin in organ culture: role for insulin-like growth factor-1 receptor and epidermal growth factor receptor. Arch. Dermatol. Res. 291, 643–651 (1999).

    Article  CAS  PubMed  Google Scholar 

  59. Philpott M. P. & Kealey T. Effects of EGF on the morphology and patterns of DNA synthesis in isolated human hair follicles. J. Invest. Dermatol. 102, 186–191 (1994).

    Article  CAS  PubMed  Google Scholar 

  60. Fish, E. N., Ghislain, J., Trogadis, J. & Stevens, J. K. Inhibitory effects of α-interferon on epidermal growth factor-mediated receptor-dependent events. Cancer Res. 53, 5148–5157 (1993).

    CAS  PubMed  Google Scholar 

  61. Graves, J. E., Jones, B. F., Lind, A. C. & Heffernan, M. P. Nonscarring inflammatory alopecia associated with the epidermal growth factor receptor inhibitor gefitinib. J. Am. Acad. Dermatol. 55, 349–353 (2006).

    Article  PubMed  Google Scholar 

  62. Mak, K. K. & Chan, S. Y. Epidermal growth factor as a biologic switch in hair growth cycle. J. Biol. Chem. 278, 26120–26126 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Hansen L. A. et al. Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am. J. Pathol. 150, 1959–1975 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Westgate G. E., Craggs R. I. & Gibson W. T. Immune privilege in hair growth. J. Invest. Dermatol. 97, 417–420 (1991).

    Article  CAS  PubMed  Google Scholar 

  65. Heck D., E., Laskin D., L., Gardner C., R. & Laskin J., D. Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes: potential role for nitric oxide in the regulation of wound healing. J. Biol. Chem. 267, 21277–21280 (1992).

    Article  CAS  PubMed  Google Scholar 

  66. Nakano, J. & Nakamura, M. Paronychia induced by gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor. J. Dermatol. 30, 261–262 (2003)

    Article  PubMed  Google Scholar 

  67. Dainichi, T., Tanaka, M., Tsuruta, N., Furue, M. & Noda, K. Development of multiple paronychia and periungual granulation in patients treated with gefitinib, an inhibitor of epidermal growth factor receptor. Dermatology 207, 324–325 (2003).

    Article  PubMed  Google Scholar 

  68. Baran R. Etretinate and the nails (study of 130 cases) possible mechanisms of some side-effects. Clin. Exp. Dermatol. 11, 148–152 (1986).

    Article  CAS  PubMed  Google Scholar 

  69. Rhee, J., Oishi, K., Garey, J. & Kim, E. Management of rash and other toxicities in patients treated with epidermal growth factor receptor-targeted agents. Clin. Colorectal Cancer 5, S101–S106 (2005).

    Article  CAS  PubMed  Google Scholar 

  70. Perez-Soler, R. et al. HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist 10, 345–356 (2005). A group of experts who study the EGFRI-induced rash indicate the importance of the rash in treated patientsand make rational recommendations for its management.

    Article  CAS  PubMed  Google Scholar 

  71. Jost, M., Huggett, T. M., Kari, C. & Rodeck, U. Matrix-independent survival of human keratinocytes through an EGF receptor/MAPK-kinase-dependent pathway. Mol. Biol. Cell 12, 1519–1527 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lopez-Ilasaca, M. et al. Effects of FK506-binding protein 12 and FK506 on autophosphorylation of epidermal growth factor receptor. J. Biol. Chem. 273, 9430–9434 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. Perez-Soler, R., Zou, Y., Li, T., Tornos, C. & Ling, Y. Topical vitamin K3 (Vit K3, Menadione) prevents erlotinib and cetuximab-induced EGFR inhibition in the skin. J. Clin. Oncol. 24, 3036 (2006).

    Article  Google Scholar 

  74. Gutzmer, R., Werfel, T., Mao, R., Kapp, A. & Elsner, J. Successful treatment with oral isotretinoin of acneiform skin lesions associated with cetuximab therapy. Br. J. Dermatol. 153, 849–851 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Segaert, S. & Van Cutsem, E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann. Oncol. 16, 1425–1433 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Sapadin, A. N. & Fleischmajer, R. Tetracyclines: nonantibiotic properties and their clinical implications. J. Am. Acad. Dermatol. 54, 258–265 (2006).

    Article  PubMed  Google Scholar 

  77. Onoda, T., Ono, T., Dhar, D. K., Yamanoi, A. & Nagasue N. Tetracycline analogues (doxycycline and COL-3) induce caspase-dependent and -independent apoptosis in human colon cancer cells. Int. J. Cancer 118, 1309–1315 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Fox, L. P. Pathology and management of dermatologic toxicities associated with anti-EGFR therapy. Oncology 20, 26–34 (2006).

    PubMed  Google Scholar 

  79. Laux, I., Jain, A., Singh, S. & Agus, D. B. Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies. Br. J. Cancer 94, 85–92 (2006).

    Article  CAS  PubMed  Google Scholar 

  80. Perea, S. et al. Genotypic bases of EGFR inhibitors pharmacological actions. J. Clin. Oncol. 22, 3005 (2004).

    Article  Google Scholar 

  81. Hidalgo., M. et al. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J. Clin. Oncol. 19, 3267–3279 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Lenz, H. J. Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events. Oncology 20, 5–13 (2006).

    PubMed  Google Scholar 

  83. Lacouture, M. E., Basti, S., Patel, J. & Benson A. The SERIES Clinic: an interdisciplinary approach to the management of toxicities to EGFR inhibitors. J. Support. Oncol. 4, 236–238 (2006). A novel interdisciplinary approach to the management of EGFR-inhibitor skin toxicities is proposed, using a patient case as a model. Early intervention and close follow-up are key strategies to prevent alterations in the anticancer agent.

    PubMed  Google Scholar 

  84. Tullo, A. B. et al. Ocular findings in patients with solid tumours treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Phase I and II clinical trials. Eye 19, 729–738 (2005).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

I would like to thank A. Paller for critically reviewing this manuscript. M.E.L. is supported by a Zell Scholarship from the Robert H. Lurie Comprehensive Cancer Center.

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  1. Department of Dermatology and Robert H. Lurie Comprehensive Cancer Center, SERIES Clinic and Cancer Skin Care Program, Northwestern University Feinberg School of Medicine, 676 North Saint Clair Suite 1600, Chicago, 60611, Illinois, USA

    Mario E. Lacouture

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DATABASES

National Cancer Institute

cervical carcinoma

colorectal cancer

squamous-cell carcinoma

FURTHER INFORMATION

Chicago Supportive Oncology

Multinational Association of Supportive Care in Cancer

Northwestern University General and Specialty Medical Dermatology Services

People Living With Cancer

Robert H. Lurie Comprehensive Cancer Center

UK National Cancer Research Institute

Glossary

Cornified envelope

The main protective barrier of the skin. It is synthesized during the late stages of keratinocyte differentiation and is composed of structural proteins, including involucrin, loricrin and small proline-rich proteins.

Antibody-dependent cell-mediated cytotoxicity

Effector cells interact with the Fc region of antibodies on a target cell's surface to mediate cell killing.

Nociceptive fibres

Afferent sensory fibres in the skin that conduct pain signals after injury or inflammation following mechanical, thermal and chemical stimuli.

Papule

A small solid rounded lesion that arises from the skin and is usually less than 5 mm in diameter. This elevation is due to metabolic deposits or the accumulation of cells.

Pustule

A small amount of purulent exudate in the top layer of skin (epidermis) or just beneath it in the dermis. Pustules frequently form in sweat glands or hair follicles. Pus is composed of leukocytes and can either contain cellular debris or bacteria, or be sterile.

Paronychium

The tissue that surrounds the nails. Underlying it is the nail matrix, which is an extension of the epidermis that is responsible for the formation of the nail plate.

Crusts

When serum, blood or pus dries on the skin surface, hardened deposits known as crusts are formed. They are yellow when derived from serum, or yellow-green-brown when derived from pus.

Telangiectasias

Dilated superficial blood vessels in the skin.

Electrodesiccation

A tissue-destructive method by which the application of a high-frequency electric current with a needle-sharp electrode destroys tissue and controls bleeding.

Xerosis

The term for dry skin. The permeability barrier is maintained by the stratum corneum.

CA-repeat polymorphisms

Population-based variations in simple sequence repeats of the dinucleotides cysteine and adenosine that modulate EGFR gene activity.

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Lacouture, M. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 6, 803–812 (2006). https://doi.org/10.1038/nrc1970

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