Journal Article

DKFZ-2025-01319

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Gene context drift identifies drug targets to mitigate cancer treatment resistance.

Jassim, A. ; Nimmervoll, B. V. ; Terranova, S. ; Nathan, E. ; Hu, L. ; Taylor, J. T. ; Masih, K. E. ; Ruff, L. ; Duarte, M. ; Cooper, E. ; Katyal, G. ; Akhbari, M. ; Gilbertson, R. J. ; Coleman, J. C. ; Toker, J. S. ; Terhune, C. ; Balmus, G. ; Jackson, S. P. ; Liu, H. ; Jiang, T. ; Taylor, M. D. ; Hua, K. ; Abraham, J. E. ; Filbin, M. G. ; Hill, A.DKFZ* ; Patrizi, A.DKFZ* ; Dani, N. ; Regev, A. ; Lehtinen, M. K. ; Gilbertson, R. J.

2025
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.ccell.2025.06.005

Abstract: Cancer treatment often fails because combinations of different therapies evoke complex resistance mechanisms that are hard to predict. We introduce REsistance through COntext DRift (RECODR): a computational pipeline that combines co-expression graph networks of single-cell RNA sequencing profiles with a graph-embedding approach to measure changes in gene co-expression context during cancer treatment. RECODR is based on the idea that gene co-expression context, rather than expression level alone, reveals important information about treatment resistance. Analysis of tumors treated in preclinical and clinical trials using RECODR unmasked resistance mechanisms -invisible to existing computational approaches- enabling the design of highly effective combination treatments for mice with choroid plexus carcinoma, and the prediction of potential new treatments for patients with medulloblastoma and triple-negative breast cancer. Thus, RECODR may unravel the complexity of cancer treatment resistance by detecting context-specific changes in gene interactions that determine the resistant phenotype.

Keyword(s): DNA repair ; cancer ; choroid plexus ; choroid plexus carcinoma ; combination therapy ; graph networks ; machine learning ; radiation ; treatment resistance ; triple-negative breast cancer

Note: epub

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Contributing Institute(s):

1. A320 NWG Neuronal signaling and morphogenesis (A320)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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