Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature

Abstract

Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFβ and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors’ proliferative index (Ki67) increased from 5–6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.

Key words

prolactinoma - aggressive - invasive - malignant - molecular endocrinology

Publikationsverlauf

Eingereicht: 27. Januar 2021

Angenommen nach Revision: 27. Mai 2021

Artikel online veröffentlicht:
19. Juli 2021

• References

• 1 Strowd RE, Salvatori R, Laterra JJ. Temozolomide retreatment in a recurrent prolactin-secreting pituitary adenoma: Hormonal and radiographic response. J Oncol Pharm Pract 2016; 22: 517-522
• 2 Zhao L, Lin M, Wang S. Identification of human prolactinoma related genes by DNA microarray. J Cancer Res Ther 2014; 10: 544-548
• 3 Sahakian N, Castinetti F, Dufour H. et al. Clinical management of difficult to treat macroprolactinomas. Expert Rev Endocrinol Metab 2019; 14: 179-192
• 4 Trouillas J, Delgrange E, Wierinckx A. et al. Clinical, Pathological, and Molecular Factors of Aggressiveness in Lactotroph Tumours. Neuroendocrinology 2019; 109: 70-76
• 5 Phillips J, East HE, French SE. et al. What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?. Hormones (Athens) 2012; 11: 477-482
• 6 Molitch ME. Management of medically refractory prolactinoma. J Neurooncol 2014; 117: 421-428
• 7 Basaran R, Onoz M, Bolukbasi FH. et al. Low O6-Methylguanine-DNA Methytransferase (mgmt) and Pan-Cytokeratin (Pan-Ck) expression via immunohistochemistry in pituitary adenomas. Acta Endocrinol (Buchar) 2017; 13: 282-293
• 8 Chen C, Yin S, Zhang S. et al. Treatment of aggressive prolactinoma with temozolomide: A case report and review of literature up to date. Medicine (Baltimore) 2017; 96: e8733
• 9 Elmaci I, Altinoz MA, Sav A. et al. Whorling-sclerosing meningioma. A review on the histological features of a rare tumor including an illustrative case. Clin Neurol Neurosurg 2017; 162: 85-90
• 10 Popadić A, Witzmann A, Buchfelder M. et al. Malignant prolactinoma: case report and review of the literature. Surg Neurol 1999; 51: 47-54
• 11 Petrossians P, de Herder W, Kwekkeboom D. et al. Malignant prolactinoma discovered by D2 receptor imaging. J Clin Endocrinol Metab 2000; 85: 398-401
• 12 Moisi M, Cruz AS, Benkers T. et al. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review. Cureus 2016; 8: e658
• 13 Ježková J, Hána V, Kosák M. et al. Role of gamma knife radiosurgery in the treatment of prolactinomas. Pituitary 2019; 22: 411-421
• 14 Lasolle H, Cortet C, Castinetti F. et al. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. Eur J Endocrinol 2017; 176: 769-777
• 15 Tang H, Cheng Y, Huang J. et al. Case Report: Temozolomide Treatment of Refractory Prolactinoma Resistant to Dopamine Agonists. Front Endocrinol (Lausanne) 2021; 12: 616339
• 16 Halevy C, Whitelaw BC. How effective is temozolomide for treating pituitary tumours and when should it be used?. Pituitary 2017; 20: 261-266
• 17 Murakami M, Mizutani A, Asano S. et al. A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: Case report. Neurosurgery 2011; 68: E1761-E1767
• 18 Dai C, Liu X, Ma W. et al. The Treatment of Refractory Pituitary Adenomas. Front Endocrinol (Lausanne) 2019; 10: 334
• 19 Giuffrida G, Ferraù F, Laudicella R. et al. Peptide receptor radionuclide therapy for aggressive pituitary tumors: A monocentric experience. Endocr Connect 2019; 8: 528-535
• 20 Faraoni EY, Camilletti MA, Abeledo-Machado A. et al. Sex differences in the development of prolactinoma in mice overexpressing hCGβ: Role of TGFβ1. J Endocrinol 2017; 232: 535-546
• 21 Mahboobifard F, Bidari-Zerehpoosh F, Davoudi Z. et al. Expression patterns of ERα66 and its novel variant isoform ERα36 in lactotroph pituitary adenomas and associations with clinicopathological characteristics. Pituitary 2020; 23: 232-245
• 22 Li C, Xie W, Rosenblum JS. et al. Somatic SF3B1 hotspot mutation in prolactinomas. Nat Commun 2020; 11: 2506
• 23 Cunha FS, Domenice S, Câmara VL. et al. Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy. Andrologia 2015; 47: 680-684
• 24 Šošić-Jurjević B, Ajdžanović V, Miljić D. et al. Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens-An Insight From Translational Studies. Int J Mol Sci 2020; 21: 2024
• 25 Ahtiainen P, Sharp V, Rulli SB. et al. Enhanced LH action in transgenic female mice expressing hCGbeta-subunit induces pituitary prolactinomas; the role of high progesterone levels. Endocr Relat Cancer 2010; 17: 611-621
• 26 Liu J, Han H, Lu W. et al. 17β-estradiol binding to ERα promotes the progression of prolactinoma through estrogen-response element-induced CaBP-9k up-regulation. Biosci Rep 2020; 40: BSR20191330
• 27 Souteiro P, Karavitaki N. Dopamine agonist resistant prolactinomas: any alternative medical treatment?. Pituitary 2020; 23: 27-37
• 28 Su YX, Du GL, Shen HL. et al. Increased expression of aromatase cytochrome P450 enzyme is associated with prolactinoma invasiveness in post-menopausal women. J Int Med Res 2019; 47: 3115-3126
• 29 Choudhary C, Hamrahian AH, Bena JF. et al. The effect of raloxifene on serum prolactin level in patients wıth prolactinoma. Endocr Pract 2019; 25: 684-688
• 30 Cao L, Gao H, Gui S. et al. Effects of the estrogen receptor antagonist fulvestrant on F344 rat prolactinoma models. J Neurooncol 2014; 116: 523-531
• 31 Wang C, Bai M, Wang X. et al. Estrogen receptor antagonist fulvestrant inhibits proliferation and promotes apoptosis of prolactinoma cells by regulating the IRE1/XBP1 signaling pathway. Mol Med Rep 2018; 18: 4037-4041
• 32 Wang C, Xu JL, Wen Y. et al. Fulvestrant inhibits the glycolysis of prolactinoma GH3 cells by downregulating IRE1/XBP1 signaling pathway. Eur Rev Med Pharmacol Sci 2018; 22: 5364-5370
• 33 Chen R, Duan J, Li L. et al. mTOR promotes pituitary tumor development through activation of PTTG1. Oncogene 2017; 36: 979-988
• 34 Recouvreux MV, Camilletti MA, Rifkin DB. et al. The pituitary TGFβ1 system as a novel target for the treatment of resistant prolactinomas. J Endocrinol 2016; 228: R73-R83
• 35 Hu B, Mao Z, Jiang X. et al. Role of TGF-β1/Smad3-mediated fibrosis in drug resistance mechanism of prolactinoma. Brain Res 2018; 1698: 204-212
• 36 Camilletti MA, Abeledo-Machado A, Perez PA. et al. mPRs represent a novel target for PRL inhibition in experimental prolactinomas. Endocr Relat Cancer 2019; 26: 497-510
• 37 Coopmans EC, van Meyel SWF, Pieterman KJ. et al. Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma. Eur J Endocrinol 2019; 181: K21-K27
• 38 Lasolle H, Vasiljevic A, Borson-Chazot F. et al. Pasireotide: A potential therapeutic alternative for resistant prolactinoma. Ann Endocrinol (Paris) 2019; 80: 84-88
• 39 Cooper O, Mamelak A, Bannykh S. et al. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors. Endocrine 2014; 46: 318-327
• 40 Ben-Shlomo A, Cooper O. Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from bench to bedside. Curr Opin Endocrinol Diabetes Obes 2017; 24: 301-305
• 41 Cooper O, Bonert VS, Rudnick J. et al. EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas. J Clin Endocrinol Metab 2021; 106: e917-e925
• 42 Sorrentino A, Rienzo M, Ciccodicola A. et al. Human PRDM2: Structure, function and pathophysiology. Biochim Biophys Acta Gene Regul Mech. 2018 pii S1874
• 43 Gao H, Wang F, Lan X. et al. Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas. BMC Cancer 2015; 15: 272
• 44 Aydin B, Arslan S, Bayraklı F. et al. miRNA-mediated Drug Repurposing Unveiled Potential Candidate Drugs for Prolactinoma Treatment. Neuroendocrinology 2021;
• 45 Chen R, Duan J, Li L. et al. mTOR promotes pituitary tumor development through activation of PTTG1. Oncogene 2017; 36: 979-988
• 46 Geng X, Ma L, Li Z. et al. Bromocriptine Induces Autophagy-Dependent Cell Death in Pituitary Adenomas. World Neurosurg 2017; 100: 407-416
• 47 Zhang D, Way JS, Zhang X. et al. Effect of Everolimus in Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas. J Clin Endocrinol Metab 2019; 104: 1929-1936
• 48 Gorvin CM, Newey PJ, Rogers A. et al. Association of prolactin receptor (PRLR) variants with prolactinomas. Hum Mol Genet 2019; 28: 1023-1037