Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma
Joint Authors
Sigala, Sandra
Fiorentini, Chiara
Grisanti, Salvatore
Cosentini, Deborah
Abate, Andrea
Rossini, Elisa
Berruti, Alfredo
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-01
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
Adrenocortical carcinoma (ACC) is a rare, highly aggressive cancer, often insensitive to conventional chemotherapeutics agents.
Early diagnosis, followed by radical surgical resection plus/minus adjuvant mitotane therapy, is nowadays the only valuable option.
Unfortunately, one out of four patients has metastatic disease at diagnosis and most of radically resected ACC patients are destined to recur with local or metastatic disease.
Numerous efforts aimed at identifying molecular alterations crucial for ACC pathogenesis have been extensively conducted, with the hope to develop new treatments.
Indeed, multiple genes and pathways have been identified as potentially targetable in ACC patients; however, despite the strong preclinical rationale, translational findings to clinical trials led to date to disappointing results.
The immunotherapeutic intervention targeting T-cell checkpoint molecules has been proposed as well, but results obtained in early studies indicate that ACC patients would be unlikely to benefit from immunotherapy.
Genetic alterations of different pathways involved in ACC carcinogenesis are also known substrates of resistance to immunotherapy.
Among them, β-catenin gene CTNNB1 and TP53 gene are frequently mutated in ACC samples.
Overactivation of the β-catenin pathway and loss of p53 protein function are potential tumor-intrinsic factors that, impacting on the ability of ACC cells to recruit dendritic cells, leading to T-cell exclusion, put this tumor among those that are potentially resistant to immunotherapy.
Moreover, the steroid phenotype, which implies glucocorticoids hypersecretion in a subset of ACC, contributes to generating an immunosuppressive microenvironment.
Here, we review clinical results of immunotherapy in ACC and we highlight molecular mechanisms driving immunotherapy failure in ACC, suggesting possible approaches to overcome resistance.
American Psychological Association (APA)
Fiorentini, Chiara& Grisanti, Salvatore& Cosentini, Deborah& Abate, Andrea& Rossini, Elisa& Berruti, Alfredo…[et al.]. 2019. Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma. Journal of Oncology،Vol. 2019, no. 2019, pp.1-7.
https://search.emarefa.net/detail/BIM-1184385
Modern Language Association (MLA)
Fiorentini, Chiara…[et al.]. Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma. Journal of Oncology No. 2019 (2019), pp.1-7.
https://search.emarefa.net/detail/BIM-1184385
American Medical Association (AMA)
Fiorentini, Chiara& Grisanti, Salvatore& Cosentini, Deborah& Abate, Andrea& Rossini, Elisa& Berruti, Alfredo…[et al.]. Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma. Journal of Oncology. 2019. Vol. 2019, no. 2019, pp.1-7.
https://search.emarefa.net/detail/BIM-1184385
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1184385