| Added by | lklinares |
|---|---|
| Group name | EquipeLL |
| Item Type | Journal Article |
| Title | Combining the antianginal drug perhexiline with chemotherapy induces complete pancreatic cancer regression in vivo |
| Creator | Reyes-Castellanos et al. |
| Author | Gabriela Reyes-Castellanos |
| Author | Nadine Abdel Hadi |
| Author | Scarlett Gallardo-Arriaga |
| Author | Rawand Masoud |
| Author | Julie Garcia |
| Author | Sophie Lac |
| Author | Abdessamad El Kaoutari |
| Author | Tristan Gicquel |
| Author | Mélanie Planque |
| Author | Sarah-Maria Fendt |
| Author | Laetitia Karine Linares |
| Author | Odile Gayet |
| Author | Fabienne Guillaumond |
| Author | Nelson Dusetti |
| Author | Juan Iovanna |
| Author | Alice Carrier |
| Abstract | Pancreatic ductal adenocarcinoma (PDAC) remains one of the human cancers with the poorest prognosis. Interestingly, we found that mitochondrial respiration in primary human PDAC cells depends mainly on the fatty acid oxidation (FAO) to meet basic energy requirements. Therefore, we treated PDAC cells with perhexiline, a well-recognized FAO inhibitor used in cardiac diseases. Some PDAC cells respond efficiently to perhexiline, which acts synergistically with chemotherapy (gemcitabine) in vitro and in two xenografts in vivo. Importantly, perhexiline in combination with gemcitabine induces complete tumor regression in one PDAC xenograft. Mechanistically, this co-treatment causes energy and oxidative stress promoting apoptosis but does not exert inhibition of FAO. Yet, our molecular analysis indicates that the carnitine palmitoyltransferase 1C (CPT1C) isoform is a key player in the response to perhexiline and that patients with high CPT1C expression have better prognosis. Our study reveals that repurposing perhexiline in combination with chemotherapy is a promising approach to treat PDAC. |
| Publication | iScience |
| Volume | 26 |
| Issue | 6 |
| Pages | 106899 |
| Date | 2023-06-16 |
| Journal Abbr | iScience |
| Language | eng |
| DOI | 10.1016/j.isci.2023.106899 |
| ISSN | 2589-0042 |
| Library Catalog | PubMed |
| Extra | PMID: 37305702 PMCID: PMC10250830 |
| Tags | Biological sciences, Cancer systems biology, original |
| Date Added | 2024/12/03 - 09:12:56 |
| Date Modified | 2024/12/03 - 09:12:56 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
