Gvozdar, Ernes

Jensen, Elisa Pouline

Jørgensen, Sara Rubek

Nielsen, Sofie Sylvest

Nonboe, Annika Weile

Lapatinib is a new drug used in treatment of breast cancer, in which the human epidermal growth factor receptor 2 (HER-2) from the HER family is upregulated and activated. Lapatinib is a dual tyrosine kinase inhibitor of HER-1 and HER-2 and these receptors are involved in the control of apoptosis, cellular proliferation and differentiation. Treatment with Lapatinib has shown improved forecasts compared to previous medication. However different side effects have often been observed, such as skin rash and diarrhea. Identification of the cellular mechanisms underlying these side effects is important for optimizing treatment. Based on a literature study different causal relationships are presented, these may underlie the development of various side effects such as skin rash and diarrhea. These causal relationships are presented in 15 hypotheses, which include eight hypotheses for dermatological side effects and seven hypotheses for intestinal side effects. The 15 hypotheses include inhibition of HER, inhibition of other tyrosine kinases and metabolism of Lapatinib. It is deduced that there is a causal relationship between inhibition of HER-1 and HER-2 by Lapatinib in breast cancer and the often observed dermatological and intestinal side effects. Less supported is the possibility that Lapatinibs metabolism and Lapatinibs potential inhibition of other tyrosine kinases may affect the development of dermatological and intestinal side effects.Lapatinib is a new drug used in treatment of breast cancer, in which the human epidermal growth factor receptor 2 (HER-2) from the HER family is upregulated and activated. Lapatinib is a dual tyrosine kinase inhibitor of HER-1 and HER-2 and these receptors are involved in the control of apoptosis, cellular proliferation and differentiation. Treatment with Lapatinib has shown improved forecasts compared to previous medication. However different side effects have often been observed, such as skin rash and diarrhea. Identification of the cellular mechanisms underlying these side effects is important for optimizing treatment. Based on a literature study different causal relationships are presented, these may underlie the development of various side effects such as skin rash and diarrhea. These causal relationships are presented in 15 hypotheses, which include eight hypotheses for dermatological side effects and seven hypotheses for intestinal side effects. The 15 hypotheses include inhibition of HER, inhibition of other tyrosine kinases and metabolism of Lapatinib. It is deduced that there is a causal relationship between inhibition of HER-1 and HER-2 by Lapatinib in breast cancer and the often observed dermatological and intestinal side effects. Less supported is the possibility that Lapatinibs metabolism and Lapatinibs potential inhibition of other tyrosine kinases may affect the development of dermatological and intestinal side effects

Roskilde Universitet

Mulige årsagssammenhænge for de oftest observerede dermatologiske og intestinale bivirkninger ved behandling med Lapatinib: Possible causes of the most often observed dermatologic and intestinal side effects in treatment with Lapatinib

Mulige årsagssammenhænge for de oftest observerede dermatologiske og intestinale bivirkninger ved behandling med Lapatinib: Possible causes of the most often observed dermatologic and intestinal side effects in treatment with Lapatinib

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Roskilde Universitet