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In a June 29 article published online in Molecular Carcinogenesis, Fenton et al demonstrated that topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse.
Dasatinib is a tyrosine kinase inhibitor currently used to treat imatinib-resistant chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Its mechanism of action is to block the activity of tyrosine kinases by attaching to their adenosine triphosphate–binding site. It can inhibit the activity of the following tyrosine kinases: Src family kinases (SFK), break point cluster region-Abelson (Bcr-Abl), Ephrin type-A receptor 2 (EphA2), platelet-derived growth factor receptor, and mast/stem cell factor receptor (also called CD117 or c-Kit).
Src family kinases are associated with transformation of cells and progression of cancer. Elevated Src family kinases activity is present in the majority of human carcinomas.
Fyn, a nonreceptor tyrosine kinase, is a member of the Src family kinases. Cell growth, cell migration, and protein kinase B (Akt)–mediated inhibition of apoptosis are influenced by Fyn activity. In addition, Fyn activity is overexpressed in cutaneous squamous cell carcinoma.
In conclusion, dasatinib—an Src family kinases inhibitor—was able to inhibit Fyn activity and thereby reduce UV-induced skin carcinogenesis.
What’s the issue?
In 1962, Falkson and Schulz (Br J Dermatol. 1962;74:229-236) noted not only inflammation and subsequent resolution of actinic keratoses after exposure to sunlight in a woman with colon cancer being treated with systemic 5-fluorouracil but also several other patients whose keratoses were seen to disappear during therapy without preceding erythema. Omura and Torre (JAMA. 1969;208:150-151) confirmed these observations in a woman with breast cancer whose actinic keratoses became inflamed after receiving intravenous 5-fluorouracil and subsequently faded. The route of drug administration was modified and 5-fluorouracil was applied topically. Today topical 5-fluorouracil is still used for the treatment of actinic keratoses.
Topical application of nitrogen mustard is used in the treatment of cutaneous T-cell lymphoma. In addition, intralesional administration of systemic antineoplastic agents has been used to treat cutaneous neoplasms: methotrexate for keratoacanthomas and rituximab for primary cutaneous B-cell lymphomas.
The Fenton et al study suggests that topical dasatinib may be a potential therapeutic intervention for the treatment of cutaneous squamous cell carcinoma. The investigators not only demonstrate laboratory data from mouse studies but also provide a potential molecular mechanism for drug-associated tumor suppression. Indeed, dasatinib solution, dasatinib cream, or both may be the next innovative therapy for the suppression of cutaneous squamous cell carcinoma in organ transplant and immunocompromised patients and for the potential management of this skin cancer in immunocompetent individuals. What do you think?
In a June 29 article published online in Molecular Carcinogenesis, Fenton et al demonstrated that topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse.
Dasatinib is a tyrosine kinase inhibitor currently used to treat imatinib-resistant chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Its mechanism of action is to block the activity of tyrosine kinases by attaching to their adenosine triphosphate–binding site. It can inhibit the activity of the following tyrosine kinases: Src family kinases (SFK), break point cluster region-Abelson (Bcr-Abl), Ephrin type-A receptor 2 (EphA2), platelet-derived growth factor receptor, and mast/stem cell factor receptor (also called CD117 or c-Kit).
Src family kinases are associated with transformation of cells and progression of cancer. Elevated Src family kinases activity is present in the majority of human carcinomas.
Fyn, a nonreceptor tyrosine kinase, is a member of the Src family kinases. Cell growth, cell migration, and protein kinase B (Akt)–mediated inhibition of apoptosis are influenced by Fyn activity. In addition, Fyn activity is overexpressed in cutaneous squamous cell carcinoma.
In conclusion, dasatinib—an Src family kinases inhibitor—was able to inhibit Fyn activity and thereby reduce UV-induced skin carcinogenesis.
What’s the issue?
In 1962, Falkson and Schulz (Br J Dermatol. 1962;74:229-236) noted not only inflammation and subsequent resolution of actinic keratoses after exposure to sunlight in a woman with colon cancer being treated with systemic 5-fluorouracil but also several other patients whose keratoses were seen to disappear during therapy without preceding erythema. Omura and Torre (JAMA. 1969;208:150-151) confirmed these observations in a woman with breast cancer whose actinic keratoses became inflamed after receiving intravenous 5-fluorouracil and subsequently faded. The route of drug administration was modified and 5-fluorouracil was applied topically. Today topical 5-fluorouracil is still used for the treatment of actinic keratoses.
Topical application of nitrogen mustard is used in the treatment of cutaneous T-cell lymphoma. In addition, intralesional administration of systemic antineoplastic agents has been used to treat cutaneous neoplasms: methotrexate for keratoacanthomas and rituximab for primary cutaneous B-cell lymphomas.
The Fenton et al study suggests that topical dasatinib may be a potential therapeutic intervention for the treatment of cutaneous squamous cell carcinoma. The investigators not only demonstrate laboratory data from mouse studies but also provide a potential molecular mechanism for drug-associated tumor suppression. Indeed, dasatinib solution, dasatinib cream, or both may be the next innovative therapy for the suppression of cutaneous squamous cell carcinoma in organ transplant and immunocompromised patients and for the potential management of this skin cancer in immunocompetent individuals. What do you think?
In a June 29 article published online in Molecular Carcinogenesis, Fenton et al demonstrated that topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse.
Dasatinib is a tyrosine kinase inhibitor currently used to treat imatinib-resistant chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Its mechanism of action is to block the activity of tyrosine kinases by attaching to their adenosine triphosphate–binding site. It can inhibit the activity of the following tyrosine kinases: Src family kinases (SFK), break point cluster region-Abelson (Bcr-Abl), Ephrin type-A receptor 2 (EphA2), platelet-derived growth factor receptor, and mast/stem cell factor receptor (also called CD117 or c-Kit).
Src family kinases are associated with transformation of cells and progression of cancer. Elevated Src family kinases activity is present in the majority of human carcinomas.
Fyn, a nonreceptor tyrosine kinase, is a member of the Src family kinases. Cell growth, cell migration, and protein kinase B (Akt)–mediated inhibition of apoptosis are influenced by Fyn activity. In addition, Fyn activity is overexpressed in cutaneous squamous cell carcinoma.
In conclusion, dasatinib—an Src family kinases inhibitor—was able to inhibit Fyn activity and thereby reduce UV-induced skin carcinogenesis.
What’s the issue?
In 1962, Falkson and Schulz (Br J Dermatol. 1962;74:229-236) noted not only inflammation and subsequent resolution of actinic keratoses after exposure to sunlight in a woman with colon cancer being treated with systemic 5-fluorouracil but also several other patients whose keratoses were seen to disappear during therapy without preceding erythema. Omura and Torre (JAMA. 1969;208:150-151) confirmed these observations in a woman with breast cancer whose actinic keratoses became inflamed after receiving intravenous 5-fluorouracil and subsequently faded. The route of drug administration was modified and 5-fluorouracil was applied topically. Today topical 5-fluorouracil is still used for the treatment of actinic keratoses.
Topical application of nitrogen mustard is used in the treatment of cutaneous T-cell lymphoma. In addition, intralesional administration of systemic antineoplastic agents has been used to treat cutaneous neoplasms: methotrexate for keratoacanthomas and rituximab for primary cutaneous B-cell lymphomas.
The Fenton et al study suggests that topical dasatinib may be a potential therapeutic intervention for the treatment of cutaneous squamous cell carcinoma. The investigators not only demonstrate laboratory data from mouse studies but also provide a potential molecular mechanism for drug-associated tumor suppression. Indeed, dasatinib solution, dasatinib cream, or both may be the next innovative therapy for the suppression of cutaneous squamous cell carcinoma in organ transplant and immunocompromised patients and for the potential management of this skin cancer in immunocompetent individuals. What do you think?
