Universität zu Köln

Selenz, Carolin (2023). Tyrosine kinases as therapeutic targets and their effect on the tumour microenvironment in oncogene-driven non-small-cell lung cancer. PhD thesis, Universität zu Köln.

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Abstract

Lung cancer represents the most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Approximately 80 % of patients are non-small-cell lung cancer (NSCLC) cases. These can be further subcategorised depending on the histological and molecular composition of tumours. Oncogene-dependent NSCLC comprise a major subtype of NSCLC that harbours oncogenic driver mutations, for example in the epidermal growth factor receptor tyrosine kinase. These mutations induce aberrant activation of cell signalling, thus facilitating uncontrolled cell growth and tumorigenesis. Targeted therapy represents one essential treatment strategy that is well-established in the clinic for oncogene-driven NSCLC, for example in the form of tyrosine kinase inhibitors. Other therapy approaches, such as anti-angiogenic compounds, aim to modulate the tumour microenvironment (TME) to become less advantageous to tumour cells, thus inhibiting cancer progression. Unfortunately, highly adaptive tumour cells and the dynamic nature of the TME limit the benefits of targeted therapy due to the emergence of resistance mechanisms or suppression of immune response. Therefore, it is essential to elucidate the effects of targeted therapy on the TME to increase our understanding of the underlying mechanisms responsible for the escape of immunosurveillance and tumour progression. This thesis investigated the impact of targeted therapy on cancer cells and the TME in oncogene-driven NSCLC and evaluated the remaining difficulties associated with this therapy approach, which illustrate the need for optimisation of existing therapy options or development of alternative treatment strategies.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Selenz, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-645492
Date:	2023
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Non-small-cell lung cancer UNSPECIFIED Tumour microenvironment UNSPECIFIED Tyrosine kinase inhibitors UNSPECIFIED
Date of oral exam:	2022
Referee:	Name Academic Title Ullrich, Roland Tillmann Prof. Dr. Dr. Schumacher, Björn Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/64549