Next-generation therapies for adrenocortical carcinoma

Barbara Altieri1, Cristina L. Ronchi1,2, Matthias Kroiss1,3,4, Martin Fassnacht1,3,4
1Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
2Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
3Comprehensive Cancer Mainfranken, University of Würzburg, Würzburg, Germany
4Central Laboratory, University Hospital Würzburg, Würzburg, Germany

Tài liệu tham khảo

Fassnacht, 2013, Update in adrenocortical carcinoma, J Clin Endocrinol Metab, 98, 4551, 10.1210/jc.2013-3020 Kerkhofs, 2013, Surgery for adrenocortical carcinoma in The Netherlands: analysis of the national cancer registry data, Eur J Endocrinol, 169, 83, 10.1530/EJE-13-0142 Fassnacht, 2011, Adrenocortical carcinoma: a clinician's update, Nat Rev Endocrinol, 7, 323, 10.1038/nrendo.2010.235 Else, 2014, Adrenocortical carcinoma, Endocr Rev, 35, 282, 10.1210/er.2013-1029 Fassnacht, 2018, 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, 179, G1, 10.1530/EJE-18-0608 Fassnacht, 2009, Limited prognostic value of the 2004 International Union against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification, Cancer, 115, 243, 10.1002/cncr.24030 Libe, 2015, Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study, Ann Oncol, 26, 2119, 10.1093/annonc/mdv329 Vanbrabant, 2018, Influence of hormonal functional status on survival in adrenocortical carcinoma: systematic review and meta-analysis, Eur J Endocrinol, 179, 429, 10.1530/EJE-18-0450 Bilimoria, 2008, Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors, Cancer, 113, 3130, 10.1002/cncr.23886 Beuschlein, 2015, Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection, J Clin Endocrinol Metab, 100, 841, 10.1210/jc.2014-3182 Assie, 2014, Integrated genomic characterization of adrenocortical carcinoma, Nat Genet, 46, 607, 10.1038/ng.2953 Zheng, 2016, Comprehensive pan-genomic characterization of adrenocortical carcinoma, Canc Cell, 29, 723, 10.1016/j.ccell.2016.04.002 Lippert, 2018, Targeted molecular analysis in adrenocortical carcinomas: a strategy toward improved personalized prognostication, J Clin Endocrinol Metab, 103, 4511, 10.1210/jc.2018-01348 Fassnacht, 2010, Improved survival in patients with stage II adrenocortical carcinoma followed up prospectively by specialized centers, J Clin Endocrinol Metab, 95, 4925, 10.1210/jc.2010-0803 Amini, 2016, Curative resection of adrenocortical carcinoma: rates and patterns of postoperative recurrence, Ann Surg Oncol, 23, 126, 10.1245/s10434-015-4810-y Pommier, 1992, An eleven-year experience with adrenocortical carcinoma, Surgery, 112, 963 Megerle, 2018, Mitotane monotherapy in patients with advanced adrenocortical carcinoma, J Clin Endocrinol Metab, 103, 1686, 10.1210/jc.2017-02591 Puglisi, 2019, Mitotane concentrations influence the risk of recurrence in adrenocortical carcinoma patients on adjuvant treatment, J Clin Med, 8 Puglisi, 2020, Mitotane concentrations influence outcome in patients with advanced adrenocortical carcinoma, Cancers, vol. 12, 10.3390/cancers12030740 Hermsen, 2011, 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, 96, 1844, 10.1210/jc.2010-2676 Sbiera, 2015, Mitotane inhibits sterol-O-acyl transferase 1 triggering lipid-mediated endoplasmic reticulum stress and apoptosis in adrenocortical carcinoma cells, Endocrinology, 156, 3895, 10.1210/en.2015-1367 Hescot, 2017, Identifying mitotane-induced mitochondria-associated membranes dysfunctions: metabolomic and lipidomic approaches, Oncotarget, 8, 109924, 10.18632/oncotarget.18968 van Koetsveld, 2020, The efficacy of mitotane in human primary adrenocortical carcinoma cultures, J Clin Endocrinol Metab, 105, 407, 10.1210/clinem/dgz001 Lacombe, 2020, Sterol O-acyl transferase 1 as a prognostic marker of adrenocortical carcinoma, Cancers, 12, 10.3390/cancers12010247 Weigand, 2020, Expression of SOAT1 in adrenocortical carcinoma and response to mitotane monotherapy: an ENSAT multicenter study, Clin Endocrinol Metab, 10.1210/clinem/dgaa293 Volante, 2012, Ribonucleotide reductase large subunit (RRM1) gene expression may predict efficacy of adjuvant mitotane in adrenocortical cancer, Clin Canc Res, 18, 3452, 10.1158/1078-0432.CCR-11-2692 D'Avolio, 2013, Influence of the CYP2B6 polymorphism on the pharmacokinetics of mitotane, Pharmacogenetics Genom, 23, 293, 10.1097/FPC.0b013e3283606cb2 Ronchi, 2014, CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma, PloS One, 9, 10.1371/journal.pone.0105855 Altieri, 2020, Effects of germline CYP2W1∗6 and CYP2B6∗6 single nucleotide polymorphisms on mitotane treatment in adrenocortical carcinoma: a multicenter ENSAT study, Cancers, 12, 10.3390/cancers12020359 Fassnacht, 2012, Combination chemotherapy in advanced adrenocortical carcinoma, N Engl J Med, 366, 2189, 10.1056/NEJMoa1200966 Urup, 2013, Treatment with docetaxel and cisplatin in advanced adrenocortical carcinoma, a phase II study, Br J Canc, 108, 1994, 10.1038/bjc.2013.229 Roca, 2017, Topoisomerase 2alpha and thymidylate synthase expression in adrenocortical cancer, Endocr Relat Canc, 24, 319, 10.1530/ERC-17-0095 Ronchi, 2009, Expression of excision repair cross complementing group 1 and prognosis in adrenocortical carcinoma patients treated with platinum-based chemotherapy, Endocr Relat Canc, 16, 907, 10.1677/ERC-08-0224 Malandrino, 2010, Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma, Endocr Relat Canc, 17, 797, 10.1677/ERC-09-0341 Laufs, 2018, ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical carcinomas, Eur J Endocrinol, 178, 181, 10.1530/EJE-17-0788 Sperone, 2010, Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study, Endocr Relat Canc, 17, 445, 10.1677/ERC-09-0281 Henning, 2017, Gemcitabine-based chemotherapy in adrenocortical carcinoma: a multicenter study of efficacy and predictive factors, J Clin Endocrinol Metab, 102, 4323, 10.1210/jc.2017-01624 Lagana, 2020, Efficacy of the EDP-M scheme plus adjunctive surgery in the management of patients with advanced adrenocortical carcinoma: the Brescia experience, Cancers, 12, 10.3390/cancers12040941 Megerle, 2019, Advanced adrenocortical carcinoma - what to do when first-line therapy fails?, Exp Clin Endocrinol Diabetes, 127, 109, 10.1055/a-0715-1946 Kroiss, 2016, Salvage treatment of adrenocortical carcinoma with trofosfamide, Horm Canc, 7, 211, 10.1007/s12672-016-0260-7 Kroiss, 2019, 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, 127, 578, 10.1055/a-0747-5571 Altieri, 2019, The role of insulin-like growth factor system in the adrenocortical tumors, Minerva Endocrinol, 44, 43 Altieri, 2016, Adrenocortical tumors and insulin resistance: what is the first step?, Int J Canc, 138, 2785, 10.1002/ijc.29950 De Martino, 2019, IGF and mTOR pathway expression and in vitro effects of linsitinib and mTOR inhibitors in adrenocortical cancer, Endocrine, 64, 673, 10.1007/s12020-019-01869-1 Barlaskar, 2009, Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma, J Clin Endocrinol Metab, 94, 204, 10.1210/jc.2008-1456 Almeida, 2008, Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors, J Clin Endocrinol Metab, 93, 3524, 10.1210/jc.2008-0065 Haluska, 2010, Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma, Canc Chemother Pharmacol, 65, 765, 10.1007/s00280-009-1083-9 Naing, 2011, Phase I trial of cixutumumab combined with temsirolimus in patients with advanced cancer, Clin Canc Res, 17, 6052, 10.1158/1078-0432.CCR-10-2979 Weigel, 2014, Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children's Oncology Group, Pediatr Blood Canc, 61, 452, 10.1002/pbc.24605 Lerario, 2014, The combination of insulin-like growth factor receptor 1 (IGF1R) antibody cixutumumab and mitotane as a first-line therapy for patients with recurrent/metastatic adrenocortical carcinoma: a multi-institutional NCI-sponsored trial, Horm Canc, 5, 232, 10.1007/s12672-014-0182-1 Jones, 2015, Phase I study of intermittent oral dosing of the insulin-like growth factor-1 and insulin receptors inhibitor OSI-906 in patients with advanced solid tumors, Clin Canc Res, 21, 693, 10.1158/1078-0432.CCR-14-0265 Fassnacht, 2015, Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study, Lancet Oncol, 16, 426, 10.1016/S1470-2045(15)70081-1 Poli, 2016, Metformin as a new anti-cancer drug in adrenocortical carcinoma, Oncotarget, 7, 49636, 10.18632/oncotarget.10421 De Martino, 2019, The role of mTOR pathway as target for treatment in adrenocortical cancer, Endocr Conn, 8, R144, 10.1530/EC-19-0224 Ganesan, 2013, Phase I clinical trial of lenalidomide in combination with temsirolimus in patients with advanced cancer, Invest N Drugs, 31, 1505, 10.1007/s10637-013-0013-1 Wagle, 2014, Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib, Canc Discov, 4, 546, 10.1158/2159-8290.CD-13-0353 Mariniello, 2012, Combination of sorafenib and everolimus impacts therapeutically on adrenocortical tumor models, Endocr Relat Canc, 19, 527, 10.1530/ERC-11-0337 Kroiss, 2011, Sunitinib inhibits cell proliferation and alters steroidogenesis by down-regulation of HSD3B2 in adrenocortical carcinoma cells, Front Endocrinol, 2, 27, 10.3389/fendo.2011.00027 Berruti, 2012, Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma, Eur J Endocrinol, 166, 451, 10.1530/EJE-11-0918 Kroiss, 2012, Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial, J Clin Endocrinol Metab, 97, 3495, 10.1210/jc.2012-1419 van Erp, 2011, Mitotane has a strong and a durable inducing effect on CYP3A4 activity, Eur J Endocrinol, 164, 621, 10.1530/EJE-10-0956 Kroiss, 2011, Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma, Clin Endocrinol, 75, 585, 10.1111/j.1365-2265.2011.04214.x Takeshita, 2013, Mitotane induces CYP3A4 expression via activation of the steroid and xenobiotic receptor, J Endocrinol, 216, 297, 10.1530/JOE-12-0297 O'Sullivan, 2014, The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer, J Clin Endocrinol Metab, 99, 1291, 10.1210/jc.2013-2298 García-Donas, 2014, Phase II study of dovitinib in first line metastatic or (non resectable primary) adrenocortical carcinoma (ACC): SOGUG study 2011-03, J Clin Oncol, 32, 4588, 10.1200/jco.2014.32.15_suppl.4588 Wortmann, 2010, Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma, Eur J Endocrinol, 162, 349, 10.1530/EJE-09-0804 Phan, 2015, Hepatocyte growth factor/cMET pathway activation enhances cancer hallmarks in adrenocortical carcinoma, Canc Res, 75, 4131, 10.1158/0008-5472.CAN-14-3707 Kroiss, 2020, Objective response and prolonged disease control of advanced adrenocortical carcinoma with cabozantinib, J Clin Endocrinol Metab, 105, 10.1210/clinem/dgz318 Adam, 2010, Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome, Mod Pathol, 23, 1596, 10.1038/modpathol.2010.153 Gagliano, 2015, Inhibition of epithelial growth factor receptor can play an important role in reducing cell growth and survival in adrenocortical tumors, Biochem Pharmacol, 98, 639, 10.1016/j.bcp.2015.10.012 Quinkler, 2008, Treatment of advanced adrenocortical carcinoma with erlotinib plus gemcitabine, J Clin Endocrinol Metab, 93, 2057, 10.1210/jc.2007-2564 Samnotra VV-S, 2007, A phase II trial of gefitinib monotherapy in patients with unresectable adrenocortical carcinoma (ACC), J Clin Oncol, 25, 15527, 10.1200/jco.2007.25.18_suppl.15527 McLoughlin, 2020, Epidermal growth factor receptor mutations, Thorac Surg Clin, 30, 127, 10.1016/j.thorsurg.2020.01.008 De Martino, 2013, Molecular screening for a personalized treatment approach in advanced adrenocortical cancer, J Clin Endocrinol Metab, 98, 4080, 10.1210/jc.2013-2165 Giordano, 2009, Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling, Clin Canc Res, 15, 668, 10.1158/1078-0432.CCR-08-1067 Papadopoulos, 2017, A Phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours, Br J Canc, 117, 1592, 10.1038/bjc.2017.330 Cheng, 2016, ATR-101 disrupts mitochondrial functions in adrenocortical carcinoma cells and in vivo, Endocr Relat Canc, 23, 1, 10.1530/ERC-15-0527 LaPensee, 2016, ATR-101, a selective and potent inhibitor of acyl-CoA acyltransferase 1, induces apoptosis in H295R adrenocortical cells and in the adrenal cortex of dogs, Endocrinology, 157, 1775, 10.1210/en.2015-2052 Smith, 2020, A phase 1 study of nevanimibe HCl, a novel adrenal-specific sterol O-acyltransferase 1 (SOAT1) inhibitor, in adrenocortical carcinoma, Invest N Drugs, 10.1007/s10637-020-00899-1 Pare, 2018, Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types, Ann Oncol, 29, 2121, 10.1093/annonc/mdy335 Thorsson, 2018, The immune landscape of cancer, Immunity, 48, 812, 10.1016/j.immuni.2018.03.023 Landwehr, 2020, The interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma, J Immunother Canc, 8 Luke, 2019, WNT/beta-catenin pathway activation correlates with immune exclusion across human cancers, Clin Canc Res, 25, 3074, 10.1158/1078-0432.CCR-18-1942 Garris, 2020, Dendritic cells, the T cell-inflamed tumor microenvironment and immunotherapy treatment response, Clin Canc Res, 10.1158/1078-0432.CCR-19-1321 Fay, 2015, Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study, J Immunother Cancer, 3, 3, 10.1186/s40425-015-0047-3 Marcus, 2019, FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors, Clin Canc Res, 25, 3753, 10.1158/1078-0432.CCR-18-4070 Raymond, 2013, Adrenocortical carcinoma is a lynch syndrome-associated cancer, J Clin Oncol, 31, 3012, 10.1200/JCO.2012.48.0988 Mota, 2018, Pembrolizumab for metastatic adrenocortical carcinoma with high mutational burden: two case reports, Medicine (Baltim), 97, 10.1097/MD.0000000000013517 Lang, 2020, Development of an adrenocortical cancer humanized mouse model to characterize anti-PD1 effects on tumor microenvironment, J Clin Endocrinol Metab, 105, 10.1210/clinem/dgz014 Harrer, 2020, Disease progression after discontinuation of nivolumab for intolerable immunotherapy associated polymyalgia rheumatica in a patient with metastasized adrenocortical carcinoma: a case report and review of the literature, Clin Oncol Case Rep, 3 Gara, 2018, Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors, Nat Commun, 9, 4172, 10.1038/s41467-018-06366-z Le Tourneau, 2018, Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial, J Immunother Cancer, 6, 111, 10.1186/s40425-018-0424-9 Carneiro, 2019, Nivolumab in metastatic adrenocortical carcinoma: results of a phase 2 trial, J Clin Endocrinol Metab, 104, 6193, 10.1210/jc.2019-00600 Habra, 2019, Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma, J Immunother Cancer, 7, 253, 10.1186/s40425-019-0722-x Raj, 2020, PD-1 blockade in advanced adrenocortical carcinoma, J Clin Oncol, 38, 71, 10.1200/JCO.19.01586 Hahner, 2008, [123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes, J Clin Endocrinol Metab, 93, 2358, 10.1210/jc.2008-0050 Kreissl, 2013, [(1)(2)(3)I]Iodometomidate imaging in adrenocortical carcinoma, J Clin Endocrinol Metab, 98, 2755, 10.1210/jc.2012-3261 Hahner, 2012, [131I]iodometomidate for targeted radionuclide therapy of advanced adrenocortical carcinoma, J Clin Endocrinol Metab, 97, 914, 10.1210/jc.2011-2765 Grisanti, 2020, Treatment with 90Y/177Lu-DOTATOC in patients with metastatic adrenocortical carcinoma expressing somatostatin receptors, J Clin Endocrinol Metab, 105 Crona, 2019, Adrenocortical carcinoma - towards genomics guided clinical care, Nat Rev Endocrinol, 15, 548, 10.1038/s41574-019-0221-7 Leal, 2015, Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis, Oncotarget, 6, 43016, 10.18632/oncotarget.5513 Zhu, 2017, Rottlerin as a novel chemotherapy agent for adrenocortical carcinoma, Oncotarget, 8, 22825, 10.18632/oncotarget.15221 Satoh, 2016, Identification of niclosamide as a novel anticancer agent for adrenocortical carcinoma, Clin Canc Res, 22, 3458, 10.1158/1078-0432.CCR-15-2256 Kahn, 2014, Can we safely target the WNT pathway?, Nat Rev Drug Discov, 13, 513, 10.1038/nrd4233 Jiang, 2013, Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma, Proc Natl Acad Sci U S A, 110, 12649, 10.1073/pnas.1307218110 Koo, 2015, Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia, Proc Natl Acad Sci U S A, 112, 7548, 10.1073/pnas.1508113112 Funck-Brentano, 2018, Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice, J Endocrinol, 238, 13, 10.1530/JOE-18-0153 Ross, 2014, Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies, J Clin Pathol, 67, 968, 10.1136/jclinpath-2014-202514 Liang, 2020, Targeted gene expression profile reveals CDK4 as therapeutic target for selected patients with adrenocortical carcinoma, Front Endocrinol, 11, 219, 10.3389/fendo.2020.00219 Hadjadj, 2017, A hypothesis-driven approach identifies CDK4 and CDK6 inhibitors as candidate drugs for treatments of adrenocortical carcinomas, Aging (N Y), 9, 2695 Fiorentini, 2018, Palbociclib inhibits proliferation of human adrenocortical tumor cells, Endocrine, 59, 213, 10.1007/s12020-017-1270-0 Verma, 2016, Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3), Oncol, 21, 1165, 10.1634/theoncologist.2016-0097 Nilubol, 2018, Synergistic combination of flavopiridol and carfilzomib targets commonly dysregulated pathways in adrenocortical carcinoma and has biomarkers of response, Oncotarget, 9, 33030, 10.18632/oncotarget.26050 Ronchi, 2013, Single nucleotide polymorphism array profiling of adrenocortical tumors--evidence for an adenoma carcinoma sequence?, PloS One, 8, 10.1371/journal.pone.0073959 Ronchi, 2015, Notch1 pathway in adrenocortical carcinomas: correlations with clinical outcome, Endocr Relat Canc, 22, 531, 10.1530/ERC-15-0163 Simon, 2012, Upregulated JAG1 enhances cell proliferation in adrenocortical carcinoma, Clin Canc Res, 18, 2452, 10.1158/1078-0432.CCR-11-2371 Ran, 2017, gamma-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct, EMBO Mol Med, 9, 950, 10.15252/emmm.201607265 Cook, 2018, A phase I trial of the gamma-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma, Br J Canc, 118, 793, 10.1038/bjc.2017.495 Pereira, 2019, MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors, J Cell Biochem, 120, 894, 10.1002/jcb.27451 Kotoula, 2009, Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas, Endocr Relat Canc, 16, 565, 10.1677/ERC-08-0101 Masi, 2009, Investigation of BRAF and CTNNB1 activating mutations in adrenocortical tumors, J Endocrinol Invest, 32, 597, 10.1007/BF03346515 Tisato, 2017, MDM2/X inhibitors under clinical evaluation: perspectives for the management of hematological malignancies and pediatric cancer, J Hematol Oncol, 10, 133, 10.1186/s13045-017-0500-5 Hui, 2018, Nutlin-3a as a novel anticancer agent for adrenocortical carcinoma with CTNNB1 mutation, Canc Med, 7, 1440, 10.1002/cam4.1431 Bussey, 2016, Targeting polo-like kinase 1, a regulator of p53, in the treatment of adrenocortical carcinoma, Clin Transl Med, 5, 1, 10.1186/s40169-015-0080-3 Hoffman-Luca, 2015, Significant differences in the development of acquired resistance to the MDM2 inhibitor SAR405838 between in vitro and in vivo drug treatment, PloS One, 10, 10.1371/journal.pone.0128807 de Jonge, 2017, A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours, Eur J Canc, 76, 144, 10.1016/j.ejca.2017.02.005 Ledermann, 2014, Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial, Lancet Oncol, 15, 852, 10.1016/S1470-2045(14)70228-1 Guo, 2018, The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials, Canc Manag Res, 10, 2553 Laufer, 2012, Sonic hedgehog signaling during adrenal development, Mol Cell Endocrinol, 351, 19, 10.1016/j.mce.2011.10.002 Hasanovic, 2018, Targeting the multidrug transporter Ptch1 potentiates chemotherapy efficiency, Cells, 7, 10.3390/cells7080107 Hasanovic, 2018, Targeting the multidrug transporter Patched potentiates chemotherapy efficiency on adrenocortical carcinoma in vitro and in vivo, Int J Canc, 143, 199, 10.1002/ijc.31296 Rimkus, 2016, Targeting the sonic hedgehog signaling pathway: review of smoothened and GLI inhibitors, Cancers, 8, 10.3390/cancers8020022