Zielgerichtete Therapien in der gastrointestinalen Onkologie

In den letzten Jahren hat die Zahl der Medikamente, welche spezifische molekulare Veränderungen in Tumorzellen zielgerichtet adressieren, deutlich zugenommen. Bei Patient*innen mit gastrointestinalen Tumorerkrankungen konnte dies zu einer erheblichen Verbesserung der Prognose beitragen. Dieser Beitrag gibt einen Überblick über die aktuell verfügbaren Therapiemöglichkeiten und die jeweils zugrunde liegenden Biomarker.

Abstract

In recent years, several drugs have been approved that specifically target molecular changes in tumour cells. For patients with gastrointestinal cancer, this has contributed to a significant improvement in prognosis. This article provides an overview of the currently available treatment options and the underlying biomarkers of their mechanisms of action.

The evaluation of biomarkers and the use of targeted therapeutics have now become standard care in gastrointestinal oncology. Beyond the molecular-targeted therapy options already approved in the European Union, there is a multitude of additional drugs and biomarkers available, which can also be used outside of formal approval (so-called off-label use). Examples of this are also discussed in this overview (e.g., HER2-targeted therapy for cholangiocarcinoma, the use of KRAS^G12C inhibitors, or checkpoint inhibition in microsatellite unstable ductal pancreatic carcinoma).

The question whether the use of one of these therapeutics represents a possible treatment option for patients with gastrointestinal cancers is typically discussed in a Molecular Tumour Board after undergoing guideline-appropriate therapies.

Kernaussagen

• Patient*innen mit gastrointestinalen Tumorerkrankungen profitieren von der Zulassung molekular-zielgerichteter Medikamente.

• Bei allen gastrointestinalen Tumorerkrankungen können sowohl eine HER2-Überexpression als auch eine Mikrosatelliteninstabilität auftreten, welche jeweils mittels Immunhistochemie beurteilt werden können.

• Aufgrund der zunehmenden Anzahl von Therapien, welche auch seltene Biomarker adressieren, nimmt der Stellenwert einer breiten Multigensequenzierung zu. Es stehen dafür sowohl zugelassene als auch Off-Label-Therapieoptionen zur Verfügung.

• KRAS, das wichtigste Onkogen in der gastrointestinalen Onkologie, kann aktuell als Zielstruktur nur unzureichend therapeutisch adressiert werden.

• Bei Cholangiokarzinomen ist die Rate an Genveränderungen, welche zur Therapie genutzt werden können, besonders hoch.

Schlüsselwörter

Präzisionsonkologie - molekularpathologische Diagnostik - Genvarianten

Keywords

precision oncology - molecular diagnostics - gene variants

Publication History

Received: 19 October 2023

Accepted: 02 November 2023

Article published online:
02 April 2024

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