Universität zu Köln

Hescheler, Daniel A., Riemann, Burkhard, Hartmann, Milan J. M., Michel, Maximilian, Faust, Michael, Bruns, Christiane J., Alakus, Hakan and Chiapponi, Costanza ORCID: 0000-0002-4681-2835 (2021). Targeted Therapy of Papillary Thyroid Cancer: A Comprehensive Genomic Analysis. Front. Endocrinol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-2392

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Abstract

Background A limited number of targeted therapy options exist for papillary thyroid cancer (PTC) to date. Based on genetic alterations reported by the The Cancer Genome Atlas (TCGA), we explored whether PTC shows alterations that may be targetable by drugs approved by the FDA for other solid cancers.</p> Methods Databases of the National Cancer Institute and MyCancerGenome were screened to identify FDA-approved drugs for targeted therapy. Target genes were identified using Drugbank. Genetic alterations were classified into conferring drug sensitivity or resistance using MyCancerGenome, CiViC, TARGET, and OncoKB. Genomic data for PTC were extracted from TCGA and mined for alterations predicting drug response.</p> Results A total of 129 FDA-approved drugs with 128 targetable genes were identified. One hundred ninety-six (70%) of 282 classic, 21 (25%) of 84 follicular, and all 30 tall-cell variant PTCs harbored druggable alterations: 259 occurred in 29, 39 in 19, and 31 in 2 targetable genes, respectively. The BRAF V600 mutation was seen in 68% of classic, 16% of follicular variant, and 93% of tall-cell variant PTCs. The RET gene fusion was seen in 8% of classic PTCs, NTRK1 and 3 gene fusions in 3%, and other alterations in <2% of classic variant PTCs. Ninety-nine of 128 (77%) FDA-approved targetable genes did not show any genetic alteration in PTC. Beside selective and non-selective BRAF-inhibitors, no other FDA-approved drug showed any frequent predicted drug sensitivity (<10%).</p> Conclusion Treatment strategies need to focus on resistance mechanisms to BRAF inhibition and on genetic alteration-independent alternatives rather than on current targeted drugs.</p>

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hescheler, Daniel A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemann, Burkhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Milan J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michel, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Faust, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiapponi, Costanza UNSPECIFIED orcid.org/0000-0002-4681-2835 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-582430
DOI:	10.3389/fendo.2021.748941
Journal or Publication Title:	Front. Endocrinol.
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-2392
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RADIOACTIVE IODINE; BRAF; ASSOCIATION; MULTICENTER; SORAFENIB; INHIBITOR; CARCINOMA; EFFICACY Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58243