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Erschienen in: Wiener Medizinische Wochenschrift 13-14/2014

01.07.2014 | review

Pathways of Tumor development and progression in Drug-induced Nonmelanoma Skin Cancer: a New Hope or the Next Great Confusion?

verfasst von: Assoc. Prof. Georgi Tchernev, MD, Prof. Uwe Wollina, MD

Erschienen in: Wiener Medizinische Wochenschrift | Ausgabe 13-14/2014

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Summary

The factors that lead to the clinical manifestation of the nonmelanocytic skin tumors are different. Ultraviolet radiation, infections with human papillomaviruses, and inherited or iatrogenic-induced immunosuppression (in cases of autoimmune diseases and organ transplant recipients) are considered to be some of the most important generators and/or costimulating factors supporting the appearance of “de-novo” mutations and obstruct, in one or another way, the cell cycle arrest, the programmed cell death (apoptosis), and the immunosurveillance. Preconditions are thus created for the initial persistence and subsequent proliferation of the malignant cell branch in the genome, with the simultaneous increase of the risk of nonmelanocytic skin tumor manifestation.
A number of medical drugs that possess a currently well-known selective, targeting, and immunomodulating effect, like the TNF-alpha inhibitors for example, most probably possess an additional blocking action on the death receptors within the framework of the extrinsic apoptotic pathway. In this way, they seem to be one of the major factors for the clinical manifestation not only of nonmelanocytic skin but also of a number of other type of tumors with a dependency on the genetic predisposition of each separate patient.
This article focuses the attention on the basic exogenic and endogenic factors that affect the regulatory processes of the cellular cycle, apoptosis, immunosurveillance, and the human inflammasome in patients with nonmelanocytic skin tumors. These processes are interwoven in a complex network and are controlled by (1) the genome regulator p53, (2) its interaction with the proapoptotic acting proteins Bak and Bax, (3) as well as the interaction with the key regulatory protein of the inflammasome—ASC/TMS1.
As a process, the malignant transformation is exceptionally dynamic, plastic, and adaptive. The exterior “interferences”, on the part of the clinician, in the form of a planned therapy should be targeted at the simultaneous impact on the various pathogenetic chains with the objective of bringing the tumor cells to their total collapse. This can be made possible only after the careful and simultaneous—or parallel—examination of a much greater number of markers that serve to characterize the process of the malignant transformation—a fact, which is currently being disregarded by many researchers.
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Metadaten
Titel
Pathways of Tumor development and progression in Drug-induced Nonmelanoma Skin Cancer: a New Hope or the Next Great Confusion?
verfasst von
Assoc. Prof. Georgi Tchernev, MD
Prof. Uwe Wollina, MD
Publikationsdatum
01.07.2014
Verlag
Springer Vienna
Erschienen in
Wiener Medizinische Wochenschrift / Ausgabe 13-14/2014
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI
https://doi.org/10.1007/s10354-014-0271-3

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