Advances in adrenocortical carcinoma pharmacotherapy: what is the current state of the art?

Cremaschi, Valentina; Abate, Andrea; Cosentini, Deborah; Grisanti, Salvatore; Rossini, Elisa; Laganà, Marta; Tamburello, Mariangela; Turla, Antonella; Sigala, Sandra; Berruti, Alfredo

doi:10.1080/14656566.2022.2106128

Cited by 13 publications

(11 citation statements)

References 110 publications

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“…After multidisciplinary consultation, mitotane was selected as the first-line treatment, however, mitotane is unavailable in China. Since ProGRP is still higher than normal after surgery, we choose chemotherapy as the adjuvant treatment ( 15 ). Therefore, chemotherapy with combined etoposide and cisplatin was used as the adjuvant treatment for 4 cycles 3 weeks postoperatively.…”

Section: Treatment and Follow-upmentioning

confidence: 99%

Nonfunctional ectopic adrenocortical carcinoma in the lung: A case report and literature review

et al. 2023

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BackgroundEctopic adrenocortical tissues and neoplasms are rare and usually found in the genitourinary system and abdominal cavity. The thorax is an extremely rare ectopic site. Here, we report the first case of nonfunctional ectopic adrenocortical carcinoma (ACC) in the lung.Case presentationA 71-year-old Chinese man presented with vague left-sided chest pain and irritable cough for 1 month. Thoracic computed tomography revealed a heterogeneously enhancing 5.3 × 5.8 × 6.0-cm solitary mass in the left lung. Radiological findings suggested a benign tumor. The tumor was surgically excised upon detection. Histopathological examination using hematoxylin and eosin staining showed that the cytoplasm of the tumor cells was rich and eosinophilic. Immunohistochemical profiles (inhibin-a+, melan-A+, Syn+) indicated that the tumor had an adrenocortical origin. The patient showed no symptoms of hormonal hypersecretion. The final pathological diagnosis was non-functional ectopic ACC. The patient was disease-free for 22 months and is still under follow-up.ConclusionsNonfunctional ectopic ACC in the lung is an extremely rare neoplasm that can be easily misdiagnosed as primary lung cancer or lung metastasis, both preoperatively and on postoperative pathological examination. This report may provide clues to clinicians and pathologists regarding the diagnosis and treatment of nonfunctional ectopic ACC.

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Section: Treatment and Follow-upmentioning

confidence: 99%

Nonfunctional ectopic adrenocortical carcinoma in the lung: A case report and literature review

et al. 2023

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“…Unfortunately, the progression of advanced disease occurs almost invariably after less than 18 months and there are no defined lines of treatment (Fassnacht et al, 2012;Laganà et al, 2020) since neither molecular target agents nor immunotherapy has been shown to obtain substantial clinical benefit (Grisanti et al, 2019;Grisanti et al, 2020). New therapeutic strategies are therefore needed, and research is currently focused on finding new drugs and improving the efficacy of existing ones (Cremaschi et al, 2022).…”

Section: A Short-running Title Progesterone As a New Pharmacological ...mentioning

confidence: 99%

Preclinical evidence of progesterone as a new pharmacological strategy in human adrenocortical carcinoma cell lines

Tamburello

Abate

Rossini

et al. 2022

Preprint

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Background and Purpose: Adrenocortical cancer (ACC) is a rare malignant neoplasm with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, cisplatin). However, new therapeutic approaches for advanced ACC are needed, particularly targeting the metastatic process. Here, we deepen the role of progesterone as a new potential drug useful in ACC, in line with other studies that demonstrated its antitumoral effect in other cancers. Experimental Approach: NCI-H295R, MUC-1, and TVBF-7 ACC cell lines were used. Cell apoptosis and cell cycle were analyzed by flow cytometry. Cell migration and invasiveness were studied using transwell assays, and metalloprotease 2 activity by zymography. Cell xenografts in zebrafish embryos were performed by measuring both the tumor areas and the number of embryos with metastasis. Key Results: Progesterone exerted a long-lasting cytotoxic effect in metastatic cell lines, MUC-1 and TVBF-7. Progesterone caused apoptosis in NCI-H295R and MUC-1 cells, inducing changes in the cell cycle distribution, while autophagy was predominantly activated in TVBF-7 cells. In the zebrafish embryos, progesterone significantly reduced each ACC cell line’s xenograft tumor area and metastasis formation in embryos injected with metastatic cells. These results were confirmed in vitro, where the reduction of invasion was mediated, at least in part, by the decrease in MMP2 levels. Conclusion and Implications: Our results give support to the role of progesterone in ACC. The involvement of its analogous (megestrol acetate) in reducing ACC progression in ACC patients undergoing EDP-M therapy is now under investigation in the PESETA phase II clinical study.

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“…Targeted therapies and immunotherapy for ACC have been used in recent clinical trials with limited benefits. 7 Two major studies deciphered the genomic landscape of ACC using the French COMETE/European ENSAT cohort 8 and the American TCGA cohort. 9 Transcriptome unsupervised clustering identified two subgroups of tumors C1A and C1B with very poor and much better outcomes, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Targeted therapies and immunotherapy for ACC have been used in recent clinical trials with limited benefits. 7…”

Section: Introductionmentioning

confidence: 99%

Aberrant activation of Wnt/β-Catenin signaling pathway drives the expression of poor prognosis-associated microRNAs in adrenocortical cancer with a major impact on miR-139-5p and its host gene PDE2A

Cristante

Sayed

Denis

et al. 2023

Preprint

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Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Deregulated microRNA (miRNA) expression has been implicated in ACC aggressiveness. Nevertheless, the mechanisms underlying such deregulations remain unknown. Aberrant Wnt/β-Catenin signaling has been reported in about 40% of ACC and is associated with poor outcome. Here, we investigated the link between constitutive activation of Wnt/β-Catenin pathway and miRNA expression alterations in ACC. Inducible shRNA-mediated gene silencing of β-Catenin (β-Cat) was performed in ACC cells expressing constitutively active β-Catenin. The miRnome of ACC cells was analyzed using RNA-Sequencing. Selected miRNAs and mRNAs were validated using quantitative PCR and functional experiments with an emphasis on miR-139-5p, its host gene phosphodiesterase 2A (PDE2A) and its target gene N-Myc Downstream-Regulated Gene 4 (NDRG4). Prognostic values of Wnt/β-Catenin pathway components or mutational status and their correlations with miRNA/mRNA expressions were determined in COMETE-ENSAT and TCGA cohorts. We carried out the first miRnome analysis in β-Catenin-deficient (β-Cat-) ACC cells. Twelve upregulated miRNAs and 42 downregulated miRNAs among which miR-139-5p and miRNAs of the 14q32 locus were identified in β-Cat- cells. Downregulation of selected poor prognosis-associated miRNAs was confirmed using RT-qPCR. Remarkably, the expression of the intronic miR-139-5p was decreased by 90% in β-Cat- cells with a concomitant repression of its host gene PDE2A and upregulation of its target gene NDRG4. In ACC patients, miR-139-5p levels were highly correlated with the levels of PDE2A and anti-correlated with those of NDRG4. MiR-139-5p and PDE2A expressions were higher in patients with mutations in components of Wnt/β-Catenin signaling pathway or high expression of LEF1, with LEF1 proving a better predictor of prognosis than Wnt/β-Catenin signaling pathway mutational status. Our findings indicate that in addition to inducing protein-coding genes in ACC, constitutively active Wnt/β-Catenin signaling upregulates the expression of a subset of miRNAs involved in tumour aggressiveness and poor clinical outcome.

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Advances in adrenocortical carcinoma pharmacotherapy: what is the current state of the art?

Cited by 13 publications

References 110 publications

Nonfunctional ectopic adrenocortical carcinoma in the lung: A case report and literature review

Nonfunctional ectopic adrenocortical carcinoma in the lung: A case report and literature review

Preclinical evidence of progesterone as a new pharmacological strategy in human adrenocortical carcinoma cell lines

Aberrant activation of Wnt/β-Catenin signaling pathway drives the expression of poor prognosis-associated microRNAs in adrenocortical cancer with a major impact on miR-139-5p and its host gene PDE2A

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