Molekularpathogenese von Schilddrüsentumoren

Zusammenfassung

Die Konzepte zur Molekularpathogenese von Schilddrüsentumoren haben sich in den letzten Jahren kontinuierlich weiterentwickelt. Als entscheidender Faktor wurde in Schilddrüsenkarzinomen die konstitutive Aktivierung intrazellulärer Tyrosinkinasen identifiziert. In Follikelzell-basierten Karzinomen scheint die Aktivierung von MAPK- und PI3K-Signalkaskaden über somatische Mutationen und Gen-Rearrangements eine entscheidende Rolle zu spielen. In niedrig differenzierten und anaplastischen Karzinomen wird oftmals eine Akkumulation genetischer Veränderungen der Follikelzell-basierten Tumoren und das Auftreten neuer genetischer Mutationen beobachtet. Das C-Zell-basierte medulläre Karzinom entsteht durch eine Aktivierung der RET-Kinase über Keimbahnmutationen im RET-Proto-Onkogen oder somatische RET- und RAS-Mutationen. Die Erkenntnisse zur molekularen Pathogenese von Schilddrüsentumoren haben die Entwicklung neuer zielgerichteter Therapien ermöglichst. Die Identifikation molekularer Marker ist für eine Vorhersage hinsichtlich der Wirkung zielgerichteter Therapien wünschenswert.

Abstract

The molecular pathogenesis of thyroid tumors has been an evolving field in the past years. The constitutive activation of intracellular tyrosine kinases has been identified as a hallmark of thyroid cancer. The activation of MAPK and PI3K pathways through somatic gene mutations or gene rearrangements seem to play a pivotal role in the pathogenesis of follicular-cell-derived tumors. In poorly differentiated tumors and anaplastic tumors often an accumulation of genetic alterations from differentiated thyroid cancer but also novel gene mutations can be observed. The C-cell-derived medullary thyroid cancer evolves through the constitutive activation of the RET kinase, either through germline RET mutations or somatic RET and RAS mutations. The better knowledge of the molecular pathogenesis allowed the development of targeted therapies in thyroid cancer patients. The identification of molecular response markers to tyrosine kinase inhibitor therapy is desirable.

Schlüsselwörter

Schilddrüsenkarzinom - PI3K - MAPK - RET - zielgerichtete Therapie

Keywords

thyroid cancer - PI3K - MAPK - RET - targeted therapy

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