Universität zu Köln

Hescheler, Daniel Alexander, Hartmann, Milan Janis Michael, Riemann, Burkhard, Michel, Maximilian, Bruns, Christiane Josephine, Alakus, Hakan and Chiapponi, Costanza (2022). Anaplastic thyroid cancer: genome-based search for new targeted therapy options. Endocr. Connect., 11 (4). BRISTOL: BIOSCIENTIFICA LTD. ISSN 2049-3614

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Abstract

ObjectiveAnaplastic thyroid cancer (ATC) is one of the most lethal human cancers with meager treatment options. We aimed to identify the targeted drugs already approved by the Food and Drug Administration (FDA) for solid cancer in general, which could be effective in ATC. DesignDatabase mining. MethodsFDA-approved drugs for targeted therapy were identified by screening the databases of MyCancerGenome and the National Cancer Institute. Drugs were linked to the target genes by querying Drugbank. Subsequently, MyCancerGenome, CIViC, TARGET and OncoKB were mined for genetic alterations which are predicted to lead to drug sensitivity or resistance. We searched the Cancer Genome Atlas database (TCGA) for patients with ATC and probed their sequencing data for genetic alterations which predict a drug response. Results In the study,155 FDA-approved drugs with 136 potentially targetable genes were identified. Seventeen (52%) of 33 patients found in TCGA had at least one genetic alteration in targetable genes. The point mutation BRAF V600E was seen in 45% of patients. PIK3CA occurred in 18% of cases. Amplifications of ALK and SRC were detected in 3% of cases, respectively. Fifteen percent of the patients displayed a co-mutation of BRAF and PIK3CA. Besides BRAF-inhibitors, the PIK3CA-inhibitor copanlisib showed a genetically predicted response. The 146 (94%) remaining drugs showed no or low (under 4% cases) genetically predicted drug response. ConclusionsWhile ATC carrying BRAF mutations can benefit from BRAF inhibitors and this effect might be enhanced by a combined strategy including PIK3CA inhibitors in some of the patients, alterations in BRAFWT ATC are not directly targeted by currently FDA-approved options.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hescheler, Daniel Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Milan Janis Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemann, Burkhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Michel, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiapponi, Costanza UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-673747
DOI:	10.1530/EC-21-0624
Journal or Publication Title:	Endocr. Connect.
Volume:	11
Number:	4
Date:	2022
Publisher:	BIOSCIENTIFICA LTD
Place of Publication:	BRISTOL
ISSN:	2049-3614
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PHASE-II TRIAL; MUTATIONS; IDENTIFICATION; CARCINOMA; BRAF; MULTICENTER; SORAFENIB; DATABASE; ALK Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67374