2. Academic Validation
  3. Cytotoxic effects of targeted agent alone or with chemotherapy in the treatment of adenoid cystic carcinoma: a preclinical study

Cytotoxic effects of targeted agent alone or with chemotherapy in the treatment of adenoid cystic carcinoma: a preclinical study

  • Sci Rep. 2022 Jun 15;12(1):9951. doi: 10.1038/s41598-022-14197-8.
Teresa Savarese  # 1,  Andrea Abate  # 1,  Ram Manohar Basnet 2,  Luigi Lorini 3,  Cristina Gurizzan 3,  Michele Tomasoni 4,  Davide Lombardi 4,  Davide Tomasini 5,  Daniela Zizioli 2,  Maurizio Memo 1,  Alfredo Berruti 3,  Sara A Bonini 6,  Sandra Sigala  # 1,  Paolo Bossi  # 3
Affiliations

Affiliations

  • 1 Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
  • 2 Section of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
  • 3 Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and ASST Spedali Civili, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
  • 4 Unit of Otorhinolaryngology-Head and Neck Surgery, ASST Spedali Civili di Brescia, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
  • 5 Radiation Oncology Unit, Department of Medical and Surgical Specialties, Radiological Science and Public Health, ASST Spedali Civili of Brescia, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
  • 6 Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy. sara.bonini@unibs.it.
  • # Contributed equally.
PMID: 35705678 DOI: 10.1038/s41598-022-14197-8
Abstract

Adenoid cystic carcinoma (ACC) is a rare malignancy characterized by high incidence of relapse. When relapsing, ACC has an indolent but relentless behaviour, thus leading to a poor long-term prognosis. The treatment of choice of relapsing ACC remains surgery followed by radiotherapy, whenever feasible. Therapeutic weapons are limited to systemic drugs. The most widely used chemotherapy regimen is the combination of cisplatin and doxorubicin, however with low response rate and not long lasting; there is also a lack of alternatives for second line therapies in case of disease progression. Therefore, a more comprehensive strategy aimed at identifying at preclinical level the most promising drugs or combination is clearly needed. In this study, the cytotoxic effects of two standard chemotherapy drugs, cisplatin and doxorubicin, and of five targeted therapy-drugs was tested in vitro, on an h-TERT immortalized ACC cell line, and in vivo, on zebrafish embryos with ACC tumoral cell xenograft. Then, combinations of one standard chemotherapy drug plus one targeted therapy drug were also evaluated, in order to find the best treatment strategy for ACC. Data obtained demonstrated that both vorinostat and olaparib significantly increased the standard chemotherapy cytotoxic effects, suggesting new interesting therapeutic options for ACC.

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