Dottoressa di ricerca

ciclo: XXXVI

supervisore: Prof. Alessandro Fatica
relatore: Prof. Francesco Fazi

Titolo della tesi: Enhancing sensitivity of triple-negative breast cancer to DNA damaging therapy through chemical inhibition of the m6A methyltransferase METTL3

Among the different types of breast cancer, triple-negative breast cancer (TNBC) is the one with the most unfavourable prognosis and high risk of recurrence. Conventional chemotherapy and DNA damaging agents represent the main treatment for this cancer. TNBC is characterized by high METTL3 methyltransferase activity, and this correlates with invasiveness and metastasis. Here, we show that STM2457, a selective METTL3 catalytic inhibitor, strongly affect TNBC cells proliferation and migration in vitro and in vivo. Moreover, STM2457 strongly sensitizes TNBC cells to DNA damaging agents utilized in clinics, such as platinum-salts and the PARP1/2 inhibitor olaparib. Finally, we show that the catalytic inhibition of METTL3 significantly synergizes with DNA-damaging chemotherapy and PARP inhibitor in TNBC BRCA1/2-wild-type organoids. In conclusion, our data suggests that incorporating small-molecule inhibitors of METTL3 into standard treatment for TNBC holds significant promise, opening avenues for innovative combination targeted therapies. Indeed, this approach has the potential to enhance anti-cancer efficacy and mitigate risk of toxicities.

Produzione scientifica

11573/1696800 - 2024 - Enhancing sensitivity of triple-negative breast cancer to DNA-damaging therapy through chemical inhibition of the m6A methyltransferase METTL3
Cesaro, Bianca; Iaiza, Alessia; Piscopo, Fabio; Tarullo, Marco; Cesari, Eleonora; Rotili, Dante; Mai, Antonello; Diana, Alberto; Londero, Michela; Del Giacco, Luca; Masetti, Riccardo; Di Leone, Alba; Naro, Chiara; Masciarelli, Silvia; Fontemaggi, Giulia; Sette, Claudio; Fazi, Francesco; Fatica, Alessandro - 01f Lettera, Nota
rivista: CANCER COMMUNICATIONS (London: BioMed Central) pp. 282-286 - issn: 2523-3548 - wos: WOS:001125441200001 (1) - scopus: 2-s2.0-85179653539 (0)

11573/1713774 - 2024 - WTAP and m6A-modified circRNAs modulation during stress response in acute myeloid leukemia progenitor cells
Iaiza, A.; Mazzanti, G.; Goeman, F.; Cesaro, B.; Cortile, C.; Corleone, G.; Tito, C.; Liccardo, F.; De Angelis, L.; Petrozza, V.; Masciarelli, S.; Blandino, G.; Fanciulli, M.; Fatica, A.; Fontemaggi, G.; Fazi, F. - 01a Articolo in rivista
rivista: CELLULAR AND MOLECULAR LIFE SCIENCES (Basel: Birkhäuser 1997-) pp. 1-19 - issn: 1420-9071 - wos: WOS:001252744200001 (0) - scopus: 2-s2.0-85196641130 (0)

11573/1669066 - 2023 - Regulation of gene expression by m6Am RNA modification
Cesaro, Bianca; Tarullo, Marco; Fatica, Alessandro - 01g Articolo di rassegna (Review)
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1-13 - issn: 1422-0067 - wos: WOS:000932948600001 (11) - scopus: 2-s2.0-85147907905 (13)

11573/1674490 - 2023 - Combined inhibition of polyamine metabolism and eIF5A hypusination suppresses colorectal cancer growth through a converging effect on MYC translation
Coni, Sonia; Bordone, Rosa; Ivy, Devon Michael; Yurtsever, Zuleyha Nihan; Di Magno, Laura; D'amico, Rodrigo; Cesaro, Bianca; Fatica, Alessandro; Belardinilli, Francesca; Bufalieri, Francesca; Maroder, Marella; De Smaele, Enrico; Di Marcotullio, Lucia; Giannini, Giuseppe; Agostinelli, Enzo; Canettieri, Gianluca - 01a Articolo in rivista
rivista: CANCER LETTERS (Elsevier Science Ireland Limited:PO Box 85, Limerick Ireland:011 353 61 709600, 011 353 61 61944, EMAIL:, INTERNET:, Fax: 011 353 61 709114) pp. - - issn: 0304-3835 - wos: WOS:000955037000001 (8) - scopus: 2-s2.0-85150380153 (9)

11573/1665943 - 2022 - Multiple roles of m6A RNA modification in translational regulation in cancer
Fernandez Rodriguez, Guillermo; Cesaro, Bianca; Fatica, Alessandro - 01g Articolo di rassegna (Review)
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. - - issn: 1422-0067 - wos: WOS:000845775600001 (8) - scopus: 2-s2.0-85137683313 (11)

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