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

References

• Berruti A, Baudin E, Gelderblom H, et al. Adrenal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii131–vii138.
   PubMed Web of Science ®Google Scholar
• Fassnacht M, Dekkers OM, Else T, et al. european society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018;179(4):G1–G46.
   PubMed Web of Science ®Google Scholar
• Fassnacht M, Assie G, Baudin E, et al. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(11):1476–1490.
   PubMed Web of Science ®Google Scholar
• Turla A, Laganà M, Grisanti S, et al. Supportive therapies in patients with advanced adrenocortical carcinoma submitted to standard EDP-M regimen. Endocrine. 2022.
   PubMed Web of Science ®Google Scholar
• Libé R, Borget I, Ronchi CL, et al. Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study. Ann Oncol. 2015 Oct;26(10):2119–2125.
   PubMed Web of Science ®Google Scholar
• Waszut U, Szyszka P, Dworakowska D. Understanding mitotane mode of action. J Physiol Pharmacol. 2017 Feb;68(1):13–26.
   PubMed Web of Science ®Google Scholar
• Kerkhofs TM, Ettaieb MH, Hermsen IG, et al. Developing treatment for adrenocortical carcinoma. Endocr Relat Cancer. 2015 Dec;22(6):R325–R338.
   PubMed Web of Science ®Google Scholar
• Paragliola RM, Torino F, Papi G, et al. Role of mitotane in adrenocortical carcinoma - review and state of the art. Eur Endocrinol. 2018 Sep;14(2):62–66.
   PubMedGoogle Scholar
• Baudin E, Pellegriti G, Bonnay M, et al. Impact of monitoring plasma 1,1-dichlorodiphenildichloroethane (o,p’DDD) levels on the treatment of patients with adrenocortical carcinoma. Cancer. 2001;92(6):1385–1392.
   PubMed Web of Science ®Google Scholar
• Hermsen IG, Fassnacht M, Terzolo M, et al. Plasma concentrations of o,p′DDD, o,p′DDA, and o,p′DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: Results of a Retrospective ENS@T Multicenter Study. J Clin Endocrinol Metab. 2011;96(6):1844–1851.
   PubMed Web of Science ®Google Scholar
• Terzolo M, Baudin AE, Ardito A, et al. Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection. Eur J Endocrinol. 2013;169(3):263–270.
   PubMed Web of Science ®Google Scholar
• Robinson BG, Hales IB, Henniker AJ, et al. The effect of o,p’-DDD on adrenal steroid replacement therapy requirements. Clin Endocrinol (Oxf). 1987 Oct;27(4):437–444.
   PubMed Web of Science ®Google Scholar
• Terzolo M, Daffara F, Ardito A, et al. Management of adrenal cancer: a 2013 update. J Endocrinol Invest. 2014 Mar;37(3):207–217.
   PubMed Web of Science ®Google Scholar
• Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012;366(23):2189–2197.
   PubMed Web of Science ®Google Scholar
• Laganà M, Grisanti S, and Cosentini D, et al. Efficacy of the EDP-M scheme plus adjunctive surgery in the management of patients with advanced adrenocortical carcinoma: the Brescia experience. Cancers (Basel). 2020;12(4):941.
   PubMed Web of Science ®Google Scholar
• Berruti A, Terzolo M, Sperone P, et al. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005 Sep;12(3):657–666.
   PubMed Web of Science ®Google Scholar
• Grisanti S, Cosentini D, Laganà M, et al. Clinical prognostic factors in patients with metastatic adrenocortical carcinoma treated with second line gemcitabine plus capecitabine chemotherapy. Front Endocrinol (Lausanne). 2021;12:624102.
   PubMed Web of Science ®Google Scholar
• Henning JEK, Deutschbein T, Altieri B, et al. Gemcitabine-based chemotherapy in adrenocortical carcinoma: a Multicenter Study of Efficacy and Predictive Factors. J Clin Endocrinol Metab. 2017;102(11):4323–4332.
   PubMed Web of Science ®Google Scholar
• Sperone P, Ferrero A, Daffara F, et al. Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study. Endocr Relat Cancer. 2010 Jun;17(2):445–453.
   PubMed Web of Science ®Google Scholar
• Lerario AM, Hammer GD. Drug repurposing using high-throughput screening identifies a promising drug combination to treat adrenocortical carcinoma. Oncotarget. 2018 Sep 07;9(70):33245–33246.
   PubMedGoogle Scholar
• Boulate G, Amazit L, Naman A, et al. Potentiation of mitotane action by rosuvastatin: new insights for adrenocortical carcinoma management. Int J Oncol. 2019 Jun;54(6):2149–2156.
   PubMed Web of Science ®Google Scholar
• Trotta F, Avena P, Chimento A, et al. Statins reduce intratumor cholesterol affecting adrenocortical cancer growth. Mol Cancer Ther. 2020;19(9):1909–1921.
   PubMed Web of Science ®Google Scholar
• Fiorentini C, Fragni M, Tiberio GAM, et al. Palbociclib inhibits proliferation of human adrenocortical tumor cells. Endocrine. 2018;59(1):213–217.
   PubMed Web of Science ®Google Scholar
• Hadjadj D, Kim SJ, Denecker T, et al. A hypothesis-driven approach identifies CDK4 and CDK6 inhibitors as candidate drugs for treatments of adrenocortical carcinomas. Aging (Albany NY). 2017;9(12):2695–2716.
   PubMedGoogle Scholar
• Nilubol N, Boufraqech M, Zhang L, et al. Synergistic combination of flavopiridol and carfilzomib targets commonly dysregulated pathways in adrenocortical carcinoma and has biomarkers of response. Oncotarget. 2018;9(68):33030–33042.
   PubMedGoogle Scholar
• Abate A, Rossini E, and Tamburello M, et al. Ribociclib cytotoxicity alone or combined with progesterone and/or mitotane in in vitro adrenocortical carcinoma cells. Endocrinology. 2022;163(2):1-10.
   PubMed Web of Science ®Google Scholar
• Björkhem-Bergman L, Lindh JD, Bergman P. What is a relevant statin concentration in cell experiments claiming pleiotropic effects? Br J Clin Pharmacol. 2011 Jul;72(1):164–165.
   PubMed Web of Science ®Google Scholar
• Smith DC, Kroiss M, Kebebew E, et al. A phase 1 study of nevanimibe HCl, a novel adrenal-specific sterol O-acyltransferase 1 (SOAT1) inhibitor, in adrenocortical carcinoma. Invest New Drugs. 2020;38(5):1421–1429.
   PubMed Web of Science ®Google Scholar
• Fiorentini C, Fragni M, Perego P, et al. Antisecretive and antitumor activity of abiraterone acetate in human adrenocortical cancer: a Preclinical Study. J Clin Endocrinol Metab. 2016;101(12):4594–4602.
   PubMed Web of Science ®Google Scholar
• Gianoncelli A, Guarienti M, Fragni M, et al. Adrenocortical Carcinoma Xenograft in Zebrafish Embryos as a Model To Study the In Vivo Cytotoxicity of Abiraterone Acetate. Endocrinology. 2019;160(11):2620–2629.
   PubMed Web of Science ®Google Scholar
• Fragni M, Fiorentini C, Rossini E, et al. In vitro antitumor activity of progesterone in human adrenocortical carcinoma. Endocrine. 2019;63(3):592–601.
   PubMed Web of Science ®Google Scholar
• Rossini E, Tamburello M, Abate A, et al. Cytotoxic effect of progesterone, tamoxifen and their combination in experimental cell models of human adrenocortical cancer. Front Endocrinol (Lausanne). 2021;12:669426.
   PubMed Web of Science ®Google Scholar
• Tissier F, Cavard C, Groussin L, et al. Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Res. 2005;65(17):7622–7627.
   PubMed Web of Science ®Google Scholar
• Abate A, Rossini E, and Bonini SA, et al. Cytotoxic effect of trabectedin in human adrenocortical carcinoma cell lines and primary cells. Cancers (Basel). 2020;12(4):928.
   PubMed Web of Science ®Google Scholar
• Fragni M, Palma Lopez LP, Rossini E, et al. In vitro cytotoxicity of cabazitaxel in adrenocortical carcinoma cell lines and human adrenocortical carcinoma primary cell cultures. Mol Cell Endocrinol. 2019;498:110585.
   PubMed Web of Science ®Google Scholar
• De Martino MC, Al Ghuzlan A, Aubert S, et al. Molecular screening for a personalized treatment approach in advanced adrenocortical cancer. J Clin Endocrinol Metab. 2013 Oct;98(10):4080–4088.
   PubMed Web of Science ®Google Scholar
• Liang R, Weigand I, Lippert J, et al. Targeted gene expression profile reveals CDK4 as therapeutic target for selected patients with adrenocortical carcinoma. Front Endocrinol (Lausanne). 2020;11:219.
   PubMed Web of Science ®Google Scholar
• Altieri B, Colao A, Faggiano A. The role of insulin-like growth factor system in the adrenocortical tumors. Minerva Endocrinol. 2019 Mar;44(1):43–57.
   PubMed Web of Science ®Google Scholar
• Fassnacht M, Berruti A, Baudin E, et al. Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study. Lancet Oncol. 2015 Apr;16(4):426–435.
   PubMed Web of Science ®Google Scholar
• De Martino MC, van Koetsveld PM, Feelders RA, et al. IGF and mTOR pathway expression and in vitro effects of linsitinib and mTOR inhibitors in adrenocortical cancer. Endocrine. 2019;64(3):673–684.
   PubMed Web of Science ®Google Scholar
• Zheng S, Cherniack AD, Dewal N, et al. Comprehensive pan-genomic characterization of adrenocortical carcinoma. Cancer Cell. 2016;30(2):363.
   PubMed Web of Science ®Google Scholar
• Cerquetti L, Bucci B, Raffa S, et al. Effects of sorafenib, a tyrosin kinase inhibitor, on adrenocortical cancer. Front Endocrinol (Lausanne). 2021;12:667798.
   PubMed Web of Science ®Google Scholar
• Silveira E, Cavalcante IP, Kremer JL, et al. The tyrosine kinase inhibitor nilotinib is more efficient than mitotane in decreasing cell viability in spheroids prepared from adrenocortical carcinoma cells. Cancer Cell Int. 2018;18:29.
   PubMed Web of Science ®Google Scholar
• Mariniello B, Finco I, Sartorato P, et al. Somatostatin receptor expression in adrenocortical tumors and effect of a new somatostatin analog SOM230 on hormone secretion in vitro and in ex vivo adrenal cells. J Endocrinol Invest. 2011 Jun;34(6):e131–e138.
   PubMed Web of Science ®Google Scholar
• Germano A, Rapa I, Duregon E, et al. Tissue expression and pharmacological in vitro analyses of mTOR and SSTR pathways in adrenocortical carcinoma. Endocr Pathol. 2017 Jun;28(2):95–102.
   PubMed Web of Science ®Google Scholar
• Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018. 03. 359(6382):1350–1355.
   PubMed Web of Science ®Google Scholar
• Fiorentini C, Grisanti S, Cosentini D, et al. Molecular drivers of potential immunotherapy failure in adrenocortical carcinoma. J Oncol. 2019;2019:6072863.
   PubMed Web of Science ®Google Scholar
• Lang J, Capasso A, and Jordan KR, et al. Development of an adrenocortical cancer humanized mouse model to characterize anti-PD1 effects on tumor microenvironment. J Clin Endocrinol Metab. 2020 01;105(1):26–42.
   PubMed Web of Science ®Google Scholar
• Bertazza L, Barollo S, and Mari ME, et al. Biological effects of EF24, a curcumin derivative, alone or combined with mitotane in adrenocortical tumor cell lines. Molecules. 2019;24(12):2202.
   PubMed Web of Science ®Google Scholar
• Huang X, Liang C, Yang H, et al. Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: identification of potential candidate genes and pathways by transcriptome analysis. Oncol Lett. 2021 Jun;21(6):476.
   PubMed Web of Science ®Google Scholar
• Patti F, Palmioli A, Vitalini S, et al. Anticancer effects of wild mountain. Front Pharmacol. 2019;10:1647.
   PubMedGoogle Scholar
• Rubin B, Manso J, Monticelli H, et al. Crude extract of. Nat Prod Res. 2019 Jun;33(11):1646–1649.
   PubMed Web of Science ®Google Scholar
• Rubin B, Pilon C, Pezzani R, et al. The effects of mitotane and 1α,25-dihydroxyvitamin D. J Endocrinol Invest. 2020 Mar;43(3):357–367.
   PubMed Web of Science ®Google Scholar
• Lorini L, Grisanti S, Ambrosini R, et al. Antineoplastic activity of artemisinin in adrenocortical carcinoma. Endocrine. 2019;66(2):425–427.
   PubMed Web of Science ®Google Scholar
• Berruti A, Ferrero A, Sperone P, et al. Emerging drugs for adrenocortical carcinoma. Expert Opin Emerg Drugs. 2008 Sep;13(3):497–509.
   PubMed Web of Science ®Google Scholar
• Terzolo M, Angeli A, Fassnacht M, et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med. 2007;356(23):2372–2380.
   PubMed Web of Science ®Google Scholar
• Berruti A, Grisanti S, Pulzer A, et al. Long-term outcomes of adjuvant mitotane therapy in patients with radically resected adrenocortical carcinoma. J Clin Endocrinol Metab. 2017;102(4):1358–1365.
   PubMed Web of Science ®Google Scholar
• Terzolo M, Fassnacht M, and Perotti P, et al. Results of the ADIUVO Study, the First Randomized Trial on Adjuvant Mitotane in Adrenocortical Carcinoma Patients. J Endocr Soc. 2021;5. .
   Google Scholar
• Kimpel O, Bedrose S, Megerle F, et al. Adjuvant platinum-based chemotherapy in radically resected adrenocortical carcinoma: a cohort study. Br J Cancer. 2021;125(9):1233–1238.
   PubMed Web of Science ®Google Scholar
• Creemers SG, van Koetsveld PM, van den Dungen ES, et al. Inhibition of human adrenocortical cancer cell growth by temozolomide in vitro and the role of the MGMT gene. J Clin Endocrinol Metab. 2016;101(12):4574–4584.
   PubMed Web of Science ®Google Scholar
• Cosentini D, Badalamenti G, Grisanti S, et al. Activity and safety of temozolomide in advanced adrenocortical carcinoma patients. Eur J Endocrinol. 2019 Dec;181(6):681–689.
   PubMed Web of Science ®Google Scholar
• Cosentini D, Turla A, Carminati O, et al. Case report: exceptional response to second line temozolomide therapy in a patient with metastatic adrenocortical carcinoma. Front Endocrinol (Lausanne). 2021;12:674039.
   PubMed Web of Science ®Google Scholar
• Galsky MD, Dritselis A, Kirkpatrick P, et al. Cabazitaxel. Nat Rev Drug Discov. 2010 Sep;9(9):677–678.
   PubMed Web of Science ®Google Scholar
• Laganà M, Grisanti S, Ambrosini R, et al. Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma. ESMO Open. 2022;7(2):100422.
   PubMed Web of Science ®Google Scholar
• Unger N, Serdiuk I, Sheu SY, et al. Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal tumours. Clin Endocrinol (Oxf). 2008 Jun;68(6):850–857.
   PubMed Web of Science ®Google Scholar
• Grisanti S, Filice A, and Basile V, et al. Treatment with 90Y/177Lu-DOTATOC in patients with metastatic adrenocortical carcinoma expressing somatostatin receptors. J Clin Endocrinol Metab. 2020;105(3):e1-e5.
   PubMed Web of Science ®Google Scholar
• Hahner S, Hartrampf PE, and Mihatsch PW, et al. Targeting 11-beta hydroxylase with [131I]IMAZA - a novel approach for the treatment of advanced adrenocortical carcinoma. J Clin Endocrinol Metab. 2021;107(4): 1348–1355 .
   Web of Science ®Google Scholar
• Angelousi A, Kyriakopoulos G, Nasiri-Ansari N, et al. The role of epithelial growth factors and insulin growth factors in the adrenal neoplasms. Ann Transl Med. 2018 Jun;6(12):253.
   PubMed Web of Science ®Google Scholar
• Samnotra V, Vassilopoulou-Sellin R, and Fojo AT, et al. A phase II trial of gefitinib monotherapy in patients with unresectable adrenocortical carcinoma (ACC). J Clin Oncol. 2007;25 (18 Suppl):Abst no 15527.
   Web of Science ®Google Scholar
• Quinkler M, Hahner S, Wortmann S, et al. Treatment of advanced adrenocortical carcinoma with erlotinib plus gemcitabine. J Clin Endocrinol Metab. 2008 Jun;93(6):2057–2062.
   PubMed Web of Science ®Google Scholar
• Xu YZ, Zhu Y, Shen ZJ, et al. Significance of heparanase-1 and vascular endothelial growth factor in adrenocortical carcinoma angiogenesis: potential for therapy. Endocrine. 2011 Dec;40(3):445–451.
   PubMed Web of Science ®Google Scholar
• Wortmann S, Quinkler M, Ritter C, et al. Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma. Eur J Endocrinol. 2010 Feb;162(2):349–356.
   PubMed Web of Science ®Google Scholar
• Berruti A, Sperone P, Ferrero A, et al. Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma. Eur J Endocrinol. 2012 Mar;166(3):451–458.
   PubMed Web of Science ®Google Scholar
• O’Sullivan C, Edgerly M, Velarde M, et al. The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer. J Clin Endocrinol Metab. 2014 Apr;99(4):1291–1297.
   PubMed Web of Science ®Google Scholar
• Kroiss M, Quinkler M, Johanssen S, et al. Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol Metab. 2012 Oct;97(10):3495–3503.
   PubMed Web of Science ®Google Scholar
• Kroiss M, Megerle F, and Kurlbaum M, et al. Objective response and prolonged disease control of advanced adrenocortical carcinoma with cabozantinib. J Clin Endocrinol Metab. 2020;105(5):1461-1468.
   Web of Science ®Google Scholar
• Haluska P, Worden F, Olmos D, et al. Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma. Cancer Chemother Pharmacol. 2010 Mar;65(4):765–773.
   PubMed Web of Science ®Google Scholar
• Naing A, Lorusso P, Fu S, et al. Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma. Br J Cancer. 2013;108(4):826–830.
   PubMed Web of Science ®Google Scholar
• Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004. 04. 4(4):314–322.
   PubMed Web of Science ®Google Scholar
• Kroiss M, Deutschbein T, Schlötelburg W, et al. Treatment of refractory adrenocortical carcinoma with thalidomide: analysis of 27 Patients from the European Network for the Study of Adrenal Tumours Registry. Exp Clin Endocrinol Diabetes. 2019 Oct;127(9):578–584.
   PubMed Web of Science ®Google Scholar
• Raj N, Zheng Y, Kelly V, et al. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol. 2020;38(1):71–80.
   PubMed Web of Science ®Google Scholar
• Naing A, Meric-Bernstam F, and Stephen B, et al. Phase 2 study of pembrolizumab in patients with advanced rare cancers. J Immunother Cancer. 2020;8(1):252-261.
   Web of Science ®Google Scholar
• Habra MA, Stephen B, Campbell M, et al. Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. J Immunother Cancer. 2019;7(1):253.
   PubMed Web of Science ®Google Scholar
• Bedrose S, Miller KC, and Altameemi L, et al. Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma. J Immunother Cancer. 2020;8(2):1-6.
   PubMed Web of Science ®Google Scholar
• Carneiro BA, Konda B, Costa RB, et al. Nivolumab in metastatic adrenocortical carcinoma: results of a Phase 2 Trial. J Clin Endocrinol Metab. 2019;104(12):6193–6200.
   PubMed Web of Science ®Google Scholar
• McGregor BA, Campbell MT, Xie W, et al. Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies. Cancer. 2021;127(6):840–849.
   PubMed Web of Science ®Google Scholar
• Klein O, Senko C, Carlino MS, et al. Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538. Oncoimmunology. 2021;10(1):1908771.
   PubMed Web of Science ®Google Scholar
• Le Tourneau C, Hoimes C, Zarwan C, et al. Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial. J Immunother Cancer. 2018;6(1):111.
   PubMed Web of Science ®Google Scholar
• Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res. 2019 Jun 13;38(1):255.
   PubMed Web of Science ®Google Scholar
• Spranger S, Gajewski TF. Impact of oncogenic pathways on evasion of antitumour immune responses. Nat Rev Cancer. 2018. 03. 18(3):139–147.
   PubMed Web of Science ®Google Scholar
• Cosentini D, Grisanti S, Dalla Volta A, et al. Immunotherapy failure in adrenocortical cancer: where next? Endocr Connect. 2018;7(12):E5–E8.
   PubMed Web of Science ®Google Scholar
• Connell CM, Raby S, Beh I, et al. Cancer immunotherapy trial registrations increase exponentially but chronic immunosuppressive glucocorticoid therapy may compromise outcomes. Ann Oncol. 2017;28(7):1678–1679.
   PubMed Web of Science ®Google Scholar
• Flint TR, Janowitz T, Connell CM, et al. Tumor-induced IL-6 reprograms host metabolism to suppress anti-tumor immunity. Cell Metab. 2016;24(5):672–684.
   PubMed Web of Science ®Google Scholar
• Takebe N, Naqash AR, O’Sullivan Coyne G, et al. Safety, antitumor activity, and biomarker analysis in a phase I trial of the once-daily wee1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors. Clin Cancer Res. 2021;27(14):3834–3844.
   PubMed Web of Science ®Google Scholar
• Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: update on effectors and inhibitors. Cancer Treat Rev. 2018;62:50–60.
   PubMed Web of Science ®Google Scholar
• Claps M, Cerri S, Grisanti S, et al. Adding metyrapone to chemotherapy plus mitotane for cushing’s syndrome due to advanced adrenocortical carcinoma. Endocrine. 2018;61(1):169–172.
   PubMed Web of Science ®Google Scholar
• Yuen KCJ. Osilodrostat: a review of recent clinical studies and practical recommendations for its use in the treatment of cushing disease. Endocr Pract. 2021;27(9):956–965.
   PubMed Web of Science ®Google Scholar
• Pivonello R, Bancos I, Feelders RA, et al. Relacorilant, a selective glucocorticoid receptor modulator, induces clinical improvements in patients with Cushing syndrome: results From A Prospective, Open-Label Phase 2 Study. Front Endocrinol (Lausanne). 2021;12:662865.
   PubMed Web of Science ®Google Scholar
• Li D, Li N, Zhang YF, et al. Persistent polyfunctional chimeric antigen receptor T cells that target glypican 3 eliminate orthotopic hepatocellular carcinomas in mice. Gastroenterology. 2020;158(8):2250–2265.e20.
   PubMed Web of Science ®Google Scholar
• Berruti A, Libè R, Laganà M, et al. Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma: a multicenter retrospective study. Eur J Endocrinol. 2019;180(5):311–320.
   PubMed Web of Science ®Google Scholar
• Cosentini D, Grisanti S, Hadoux J, et al. Progression of vertebral fractures in patients with adrenocortical carcinoma undergoing mitotane therapy. J Clin Endocrinol Metab. 2022;107(5):e2167–e2176.
   PubMed Web of Science ®Google Scholar
• Wang T, Rainey WE. Human adrenocortical carcinoma cell lines. Mol Cell Endocrinol. 2012 Mar 31;351(1):58–65.
   PubMed Web of Science ®Google Scholar
• Rainey WE, Saner K, Schimmer BP. Adrenocortical cell lines. Mol Cell Endocrinol. 2004 Dec 30;228(1–2):23–38.
   PubMed Web of Science ®Google Scholar
• Kurlbaum M, Sbiera S, Kendl S, et al. Steroidogenesis in the NCI-H295 cell line model is strongly affected by culture conditions and substrain. Exp Clin Endocrinol Diabetes. 2020 Oct;128(10):672–680.
   PubMed Web of Science ®Google Scholar
• Nicolson NG, Korah R, Carling T. Adrenocortical cancer cell line mutational profile reveals aggressive genetic background. J Mol Endocrinol. 2019. 05. 62(4):179–186.
   PubMed Web of Science ®Google Scholar
• Kerkhofs TM, Derijks LJ, Ettaieb H, et al. Development of a pharmacokinetic model of mitotane: toward personalized dosing in adrenocortical carcinoma. Ther Drug Monit. 2015 Feb;37(1):58–65.
   PubMed Web of Science ®Google Scholar
• Volante M, Terzolo M, Fassnacht M, et al. Ribonucleotide reductase large subunit (RRM1) gene expression may predict efficacy of adjuvant mitotane in adrenocortical cancer. Clin Cancer Res. 2012;18(12):3452–3461.
   PubMed Web of Science ®Google Scholar
• Ambrosini R, Balli MC, and Laganà M, et al. Adrenocortical carcinoma and CT assessment of therapy response: the value of combining multiple criteria. Cancers (Basel). 2020;12(6):1395-1408.
   Web of Science ®Google Scholar
• Keenan TE, Tolaney SM. Role of immunotherapy in triple-negative breast cancer. J Natl Compr Canc Netw. 2020. 04. 18(4):479–489.
   PubMed Web of Science ®Google Scholar
• Reck M, Shankar G, Lee A, et al. Atezolizumab in combination with bevacizumab, paclitaxel and carboplatin for the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer, including patients with. Expert Rev Respir Med. 2020;14(2):125–136.
   PubMed Web of Science ®Google Scholar