Mechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments.

TitleMechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments.
Publication TypeJournal Article
Year of Publication2020
AuthorsCubuk, C, Can, FE, Peña-Chilet, M, Dopazo, J
JournalCells
Volume9
Issue7
Date Published2020 Jun 29
ISSN2073-4409
Abstract

Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such differences over the disease mechanisms or the drug action mechanisms are completely unknown. Here we applied mechanistic mathematical models of signaling activity to reveal the ultimate functional consequences that gender-specific gene expression activities have over cell functionality and fate. Moreover, we also used the mechanistic modeling framework to simulate the drug interventions and unravel how drug action mechanisms are affected by gender-specific differential gene expression. Interestingly, some cancers have many biological processes significantly affected by these gender-specific differences (e.g., bladder or head and neck carcinomas), while others (e.g., glioblastoma or rectum cancer) are almost insensitive to them. We found that many of these gender-specific differences affect cancer-specific pathways or in physiological signaling pathways, also involved in cancer origin and development. Finally, mechanistic models have the potential to be used for finding alternative therapeutic interventions on the pathways targeted by the drug, which lead to similar results compensating the downstream consequences of gender-specific differences in gene expression.

DOI10.3390/cells9071579
Alternate JournalCells
PubMed ID32610626
PubMed Central IDPMC7408716
Grant ListSAF2017-88908-R / / Ministerio de Economía y Competitividad /
PT17/0009/0006 / / Ministerio de Economía y Competitividad /
813533 / / FP7 People: Marie-Curie Actions /
676559 / / H2020 Research Infrastructures /