Inhibition of STAT3/Fanconi anemia axis by Nifuroxazide is synthetic lethal with PARP inhibitor and selectively targets breast cancer stem cells Article Swipe
Christophe Ginestier
,
Célia D. Rouault
,
Lucile Bansard
,
Elena Martínez‐Balsalobre
,
Caroline Bonnet
,
Julien Wicinski
,
Sylvain Debieu
,
Ludovic Colombeau
,
Guillaume Pinna
,
Margot Machu
,
Olivier Rosnet
,
Véronique Chevrier
,
Cornel Popovici
,
Hagay Sobol
,
Eddy Pasquier
,
Géraldine Guasch
,
Raphaël Rodriguez
,
Julie Pannequin
,
Jean‐Marc Pascussi
,
Christophe Lachaud
,
Emmanuelle Charafe‐Jauffret
,
Rémy Castellano
,
Marie Vandamme
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-4763425/v1
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-4763425/v1
The targeting of cancer stem cells (CSCs) has proven to be an effective approach for limiting tumor progression, thus necessitating the identification of new drugs with anti-CSC activity. Through a high-throughput drug repositioning screen, we identified the antibiotic Nifuroxazide (NIF) as a potent anti-CSC compound. Utilizing a click chemistry strategy, we demonstrated that NIF is a prodrug that is specifically bioactivated in breast CSCs. Mechanistically, NIF-induced CSC death is a result of a synergistic action that combines the generation of DNA interstrand crosslinks with the inhibition of the Fanconi anemia (FA) pathway activity. NIF treatment mimics FA-deficiency through the inhibition of STAT3, which we identified as a non-canonical transcription factor of FA-related genes. NIF induces a chemical HRDness in CSCs that (re)sensitizes breast cancers with innate or acquired resistance to PARP inhibitor (PARPi) in PDX models. Our results suggest that NIF may be useful in combination with PARPi for the treatment of breast tumors, regardless of their HRD status.
Related Topics
Concepts
Fanconi anemia
Cancer research
Prodrug
Cancer stem cell
Breast cancer
Synthetic lethality
Chemistry
Cancer
PARP inhibitor
Poly ADP ribose polymerase
DNA repair
Medicine
DNA
Biochemistry
Internal medicine
Polymerase
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-4763425/v1
- https://www.researchsquare.com/article/rs-4763425/latest.pdf
- OA Status
- gold
- References
- 77
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4401967308
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4401967308Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-4763425/v1Digital Object Identifier
- Title
-
Inhibition of STAT3/Fanconi anemia axis by Nifuroxazide is synthetic lethal with PARP inhibitor and selectively targets breast cancer stem cellsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-08-28Full publication date if available
- Authors
-
Christophe Ginestier, Célia D. Rouault, Lucile Bansard, Elena Martínez‐Balsalobre, Caroline Bonnet, Julien Wicinski, Sylvain Debieu, Ludovic Colombeau, Guillaume Pinna, Margot Machu, Olivier Rosnet, Véronique Chevrier, Cornel Popovici, Hagay Sobol, Eddy Pasquier, Géraldine Guasch, Raphaël Rodriguez, Julie Pannequin, Jean‐Marc Pascussi, Christophe Lachaud, Emmanuelle Charafe‐Jauffret, Rémy Castellano, Marie VandammeList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-4763425/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-4763425/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-4763425/latest.pdfDirect OA link when available
- Concepts
-
Fanconi anemia, Cancer research, Prodrug, Cancer stem cell, Breast cancer, Synthetic lethality, Chemistry, Cancer, PARP inhibitor, Poly ADP ribose polymerase, DNA repair, Medicine, DNA, Biochemistry, Internal medicine, PolymeraseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
77Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2023427658, https://openalex.org/W2051055358, https://openalex.org/W2001544973, https://openalex.org/W2023316892, https://openalex.org/W1967358345, https://openalex.org/W2157910818, https://openalex.org/W4378953806, https://openalex.org/W2102085111, https://openalex.org/W3097029961, https://openalex.org/W2763367287, https://openalex.org/W2120656656, https://openalex.org/W2614441145, https://openalex.org/W1989805762, https://openalex.org/W2115585914, https://openalex.org/W1995103178, https://openalex.org/W4220918240, https://openalex.org/W4385490576, https://openalex.org/W4385490780, https://openalex.org/W2083258699, https://openalex.org/W2019607817, https://openalex.org/W2039109621, https://openalex.org/W2593181149, https://openalex.org/W2971479094, https://openalex.org/W2965094510, https://openalex.org/W4379285544, https://openalex.org/W4225475235, https://openalex.org/W2106195342, https://openalex.org/W2345750662, https://openalex.org/W2519028131, https://openalex.org/W2979679161, https://openalex.org/W4376620208, https://openalex.org/W2152505144, https://openalex.org/W2010973115, https://openalex.org/W2895729583, https://openalex.org/W1965596803, https://openalex.org/W1542109034, https://openalex.org/W2885710132, https://openalex.org/W2208565711, https://openalex.org/W2557435811, https://openalex.org/W4210575588, https://openalex.org/W1491753399, https://openalex.org/W2049689768, https://openalex.org/W2621200238, https://openalex.org/W4382918422, https://openalex.org/W2044292152, https://openalex.org/W2903449267, https://openalex.org/W1968245004, https://openalex.org/W2400913401, https://openalex.org/W2033271892, https://openalex.org/W4313453500, https://openalex.org/W2319481506, https://openalex.org/W1987027200, https://openalex.org/W2142658272, https://openalex.org/W4362604457, https://openalex.org/W2898088739, https://openalex.org/W4386484436, https://openalex.org/W2074446011, https://openalex.org/W2565528596, https://openalex.org/W2156612784, https://openalex.org/W2534183860, https://openalex.org/W2601283876, https://openalex.org/W4223505754, https://openalex.org/W2107398189, https://openalex.org/W2473705942, https://openalex.org/W4282975734, https://openalex.org/W1973268287, https://openalex.org/W2171972386, https://openalex.org/W2130084494, https://openalex.org/W2145122380, https://openalex.org/W2620099337, https://openalex.org/W2487757405, https://openalex.org/W4280529765, https://openalex.org/W2167486320, https://openalex.org/W2135925682, https://openalex.org/W2562443513, https://openalex.org/W4214507610, https://openalex.org/W646737634 |
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