Universität zu Köln

Hescheler, Daniel Alexander, Hartmann, Milan Janis Michael, Riemann, Burkhard, Michel, Maximilian, Bruns, Christiane Josephine, Alakus, Hakan ORCID: 0000-0002-3889-3276 and Chiapponi, Costanza ORCID: 0000-0002-4681-2835 (2022). Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options. Cancers, 14 (11). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary Adrenocortical carcinoma is a rare disease for which in silico analysis may help to identify therapy options. Here, we look at the potential of already FDA-approved drugs and therapies in clinical trials based on genes mutated in ACC and genomic alterations known to be targeted by these drugs. Overall, 67% of the ACCs presented in silico drugability, especially for new emerging options such as TP53-modulating drugs or Wnt signaling pathway inhibitors. These results might help plan future clinical trials. In rare diseases such as adrenocortical carcinoma (ACC), in silico analysis can help select promising therapy options. We screened all drugs approved by the FDA and those in current clinical studies to identify drugs that target genomic alterations, also known to be present in patients with ACC. We identified FDA-approved drugs in the My Cancer Genome and National Cancer Institute databases and identified genetic alterations that could predict drug response. In total, 155 FDA-approved drugs and 905 drugs in clinical trials were identified and linked to 375 genes of 89 TCGA patients. The most frequent potentially targetable genetic alterations included TP53 (20%), BRD9 (13%), TERT (13%), CTNNB1 (13%), CDK4 (7%), FLT4 (7%), and MDM2 (7%). We identified TP53-modulating drugs to be possibly effective in 20-26% of patients, followed by the Wnt signaling pathway inhibitors (15%), Telomelysin and INO5401 (13%), FHD-609 (13%), etc. According to our data, 67% of ACC patients exhibited genomic alterations that might be targeted by FDA-approved drugs or drugs being tested in current clinical trials. Although there are not many current therapy options directly targeting reported ACC alterations, this study identifies emerging options that could be tested in clinical trials.

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 orcid.org/0000-0002-3889-3276 UNSPECIFIED Chiapponi, Costanza UNSPECIFIED orcid.org/0000-0002-4681-2835 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-673013
DOI:	10.3390/cancers14112721
Journal or Publication Title:	Cancers
Volume:	14
Number:	11
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PAN-CANCER; PHASE-II; MANAGEMENT; OSI-906; PATHWAY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67301