The role of the prolactin receptor pathway in the pathogenesis of glioblastoma: what do we know so far?

Abstract

Introduction: Prolactin (PRL) and its receptor (PRLR) have been associated with the development of hormone-dependent tumors and have been detected in glioblastoma (GBM) biopsies. GBM is the most common and aggressive primary brain tumor in adults and the prognosis for patients is dismal; hence researchers are exploring the PRLR pathway as a therapeutic target in this disease.

Areas covered: This paper explores the effects of PRLR activation on the biology of GBM, the correlation between PRL and PRLR expression and GBM progression and survival in male and female patients. Finally, we discuss how a better understanding of the PRLR pathway may allow the development of novel treatments for GBM.

Expert opinion: We propose PRL and PRLR as potential prognosis biomarkers and therapeutic targets in GBM. Local administration of PRLR inhibitors using gene therapy may offer a beneficial strategy for targeting GBM cells disseminated in the non-neoplastic brain; however, efficacy and safety require careful and extensive evaluation. The data depicted herein underline the need to (i) improve our understanding of sexual dimorphism in GBM, and (ii) develop accurate preclinical models that take into consideration different hormonal contexts, specific genetic alterations, and tumor grades.

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- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Neuroblastoma: Complete objective response to biological treatment;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

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- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.