2. Academic Validation
  3. The CAIX inhibitor SLC-0111 exerts anti-cancer activity on gastric cancer cell lines and resensitizes resistant cells to 5-Fluorouracil, taxane-derived, and platinum-based drugs

The CAIX inhibitor SLC-0111 exerts anti-cancer activity on gastric cancer cell lines and resensitizes resistant cells to 5-Fluorouracil, taxane-derived, and platinum-based drugs

  • Cancer Lett. 2023 Aug 5;216338. doi: 10.1016/j.canlet.2023.216338.
Elena Andreucci 1,  Alessio Biagioni 1,  Sara Peri 2,  Giampaolo Versienti 1,  Fabio Cianchi 3,  Fabio Staderini 4,  Lorenzo Antonuzzo 5,  Claudiu T Supuran 6,  Erika Olivo 7,  Elisa Pasqualini 7,  Luca Messerini 2,  Daniela Massi 7,  Matteo Lulli 1,  Jessica Ruzzolini 1,  Silvia Peppicelli 1,  Francesca Bianchini 1,  Nicola Schiavone 1,  Lido Calorini 1,  Lucia Magnelli 8,  Laura Papucci 1
Affiliations

Affiliations

  • 1 Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale GC Morgagni 50, 50134, Firenze, Italy.
  • 2 Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Firenze, Italy.
  • 3 Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Firenze, Italy; Unit of Digestive Surgery, Careggi University Hospital, Largo Brambilla 3, 50134, Firenze, Italy. Electronic address: fabio.cianchi@unifi.it.
  • 4 Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Firenze, Italy; Unit of Digestive Surgery, Careggi University Hospital, Largo Brambilla 3, 50134, Firenze, Italy.
  • 5 Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Firenze, Italy; Clinical Oncology Unit, Careggi University Hospital, Largo Brambilla 3, 50134, Firenze, Italy.
  • 6 Department of NEUROFARBA, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy.
  • 7 Department of Health Sciences, University of Florence, Viale Pieraccini 6, 50139, Firenze, Italy.
  • 8 Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale GC Morgagni 50, 50134, Firenze, Italy. Electronic address: lucia.magnelli@unifi.it.
PMID: 37549770 DOI: 10.1016/j.canlet.2023.216338
Abstract

Gastric Cancer (GC) is the fifth most frequent malignancy and the fourth leading cause of worldwide cancer-related death. Despite the usage of multimodal perioperative chemotherapy (pCT), GC progressively gains chemoresistance, thereby, the identification of suitable targets to overcome drug resistance is fundamental. Amongst the potential biomarkers, Carbonic Anhydrase IX (CAIX) - associated with a poor prognosis of several solid cancers - has gained the most attention. In a cohort of GC patients who received perioperative FLOT (i.e., Leucovorin, 5-Fluouracil, Docetaxel, and Oxaliplatin) or FOLFOX (i.e., Leucovorin, 5-Fluouracil, and Oxaliplatin), non-responder patients showed an increased expression of tumor CAIX compared to responder group. Moreover, GC cell lines induced to be resistant to 5-Fluouracil, Paclitaxel, Cisplatin, or the combination of 5-Fluorouracil, Oxaliplatin, and Docetaxel, overexpressed CAIX compared to the control. Accordingly, CAIX-high-expressing GC cells showed increased therapy resistance compared to low-expressing cells. Notably, SLC0111 significantly improved the therapy response of both wild-type and resistant GC cells. Overall, these data suggest a correlation between CAIX and GC drug resistance highlighting the potential of SLC-0111 in re-sensitizing GC cells to pCT.

Keywords

Carbonic anhydrase IX; Chemoresistance; Gastric cancer; Perioperative chemotherapy.

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