Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma
Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/11/7/661 |
| _version_ | 1797526821869191168 |
|---|---|
| author | Cristina Ilcus Horatiu Silaghi Carmen Emanuela Georgescu Carmen Georgiu Anca Ileana Ciurea Simona Delia Nicoara Cristina Alina Silaghi |
| author_facet | Cristina Ilcus Horatiu Silaghi Carmen Emanuela Georgescu Carmen Georgiu Anca Ileana Ciurea Simona Delia Nicoara Cristina Alina Silaghi |
| author_sort | Cristina Ilcus |
| collection | DOAJ |
| description | Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, <i>KIT</i>, <i>MAPK</i> and <i>PI3K</i> pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and <i>mTOR</i> inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas. |
| first_indexed | 2024-03-10T09:34:45Z |
| format | Article |
| id | doaj.art-d734257bdd8b40fba4de5e67182e0b70 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T09:34:45Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-d734257bdd8b40fba4de5e67182e0b702023-11-22T04:10:54ZengMDPI AGJournal of Personalized Medicine2075-44262021-07-0111766110.3390/jpm11070661Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System GerminomaCristina Ilcus0Horatiu Silaghi1Carmen Emanuela Georgescu2Carmen Georgiu3Anca Ileana Ciurea4Simona Delia Nicoara5Cristina Alina Silaghi6Department of Endocrinology, County Clinical Emergency Hospital Cluj, 3–5 Clinicilor Street, 400006 Cluj-Napoca, RomaniaDepartment of Surgery V, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaDepartment of Endocrinology, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaDepartment of Pathological Anatomy, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaDepartment of Radiology, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaDepartment of Ophthalmology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaDepartment of Endocrinology, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaIntracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, <i>KIT</i>, <i>MAPK</i> and <i>PI3K</i> pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and <i>mTOR</i> inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas.https://www.mdpi.com/2075-4426/11/7/661CNS germinomaKITRASMAPKmiRNAsradiotherapy |
| spellingShingle | Cristina Ilcus Horatiu Silaghi Carmen Emanuela Georgescu Carmen Georgiu Anca Ileana Ciurea Simona Delia Nicoara Cristina Alina Silaghi Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma Journal of Personalized Medicine CNS germinoma KIT RAS MAPK miRNAs radiotherapy |
| title | Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma |
| title_full | Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma |
| title_fullStr | Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma |
| title_full_unstemmed | Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma |
| title_short | Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma |
| title_sort | molecular pathology and targeted therapies for personalized management of central nervous system germinoma |
| topic | CNS germinoma KIT RAS MAPK miRNAs radiotherapy |
| url | https://www.mdpi.com/2075-4426/11/7/661 |
| work_keys_str_mv | AT cristinailcus molecularpathologyandtargetedtherapiesforpersonalizedmanagementofcentralnervoussystemgerminoma AT horatiusilaghi molecularpathologyandtargetedtherapiesforpersonalizedmanagementofcentralnervoussystemgerminoma AT carmenemanuelageorgescu molecularpathologyandtargetedtherapiesforpersonalizedmanagementofcentralnervoussystemgerminoma AT carmengeorgiu molecularpathologyandtargetedtherapiesforpersonalizedmanagementofcentralnervoussystemgerminoma AT ancaileanaciurea molecularpathologyandtargetedtherapiesforpersonalizedmanagementofcentralnervoussystemgerminoma AT simonadelianicoara molecularpathologyandtargetedtherapiesforpersonalizedmanagementofcentralnervoussystemgerminoma AT cristinaalinasilaghi molecularpathologyandtargetedtherapiesforpersonalizedmanagementofcentralnervoussystemgerminoma |