Universität zu Köln

Nenadic, Ilija, Staber, Janine, Dreier, Susanne, Simons, Guus, Schildgen, Verena, Brockmann, Michael and Schildgen, Oliver ORCID: 0000-0003-4297-9627 (2017). Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics. Cancers, 9 (7). BASEL: MDPI AG. ISSN 2072-6694

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Abstract

With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9000 Euro per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The current state-of-the-art ALK diagnostic procedure comprises a Fluorescent in situ Hybridization (FISH) assay accompanied by ALK inhibitor therapy (Crizotinib). The therapy success ranges between a full therapy failure and the complete remission of the tumor (i.e., healing), but the biomedical and systemic reasons for this range remain unknown so far. It appears that the variety of different ALK mutations and variants contributes to the discrepancy in therapy results. Although the major known fusion partner for ALK in NSCLC is the Echinoderm microtubule-associated protein-like 4 (EML4), of which a minimum of 15 variants have been described, an additional 20 further ALK fusion variants with other genes are known, of which three have already been found in NSCLC. We hypothesize that the wide variety of known (and unknown) ALK mutations is associated with a variable therapy success, thus rendering current companion diagnostic procedures (FISH) and therapy (Crizotinib) only partly applicable in ALK-related NSCLC treatment. In cell culture, differing sensitivity to Crizotinib has been shown for some fusion variants, but it is as yet unknown which of them are really biologically active in cancer patients, and how the respective variants affect the response to Crizotinib treatment. Moreover, it has been demonstrated that translocated ALK genes can also be observed in healthy tissues and are not compulsorily associated with tumors. Therefore, it is important to keep in mind that even for the known variants of ALK fusion genes, the biological function is not known for all variants, and that no information is available on the homogeneity of ALK fusion variants within a single tumor. These facts, in concert with data for ALK mutation prevalence and therapy outcomes of a German cohort of NSCLC patients, support the hypothesis that, by using novel companion diagnostic tools in combination with therapy outcome predictions, massive cost savings could be possible in European Health Care systems without a loss of patient care.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nenadic, Ilija UNSPECIFIED UNSPECIFIED UNSPECIFIED Staber, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreier, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Simons, Guus UNSPECIFIED UNSPECIFIED UNSPECIFIED Schildgen, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Brockmann, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Schildgen, Oliver UNSPECIFIED orcid.org/0000-0003-4297-9627 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-225663
DOI:	10.3390/cancers9070088
Journal or Publication Title:	Cancers
Volume:	9
Number:	7
Date:	2017
Publisher:	MDPI AG
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL LUNG-CANCER; GENERATION SEQUENCING DATA; HIV CORECEPTOR USAGE; CLINICAL-FEATURES; EML4-ALK FUSION; ALK; EGFR; CRIZOTINIB; ADENOCARCINOMA; TRANSLOCATION Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22566