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Project Description

Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Trilateral Retinoblastoma (TRb)

Trilateral retinoblastoma (TRb) is an unusual and intricate cancerous tumor found in children which appears as a combination of bilateral retinoblastoma and an intracranial tumor localized in the midline of the skull, commonly a primitive neuroectodermal tumor (PNET). Protheragen offers full-service development of diagnostics and therapeutics aimed at trilateral retinoblastoma.

Introduction to Trilateral Retinoblastoma (TRb)

Trilateral retinoblastoma is a type of syndrome with the triad of bilateral retinoblastoma and a midline malignancy located intracranially, usually in the pineal or suprasellar regions. It is almost uniquely present in children who have the familial type of retinoblastoma, putting genetic predisposition at the forefront of attention. Intracranial tumors are usually highly malignant PNETs which are capable of spreading through the neural channel, resulting in rapid progression and poor prognosis.

Magnetic resonance analysis of trilateral retinoblastoma.

Fig.1 Classification of pineal glands and nonpineal trilateral retinoblastoma on magnetic resonance imaging (MRI). (de Bloeme C. M., et al., 2024)

The development of TRb is associated with mutations of the retinoblastoma gene (RB1) located on chromosome 13q14. This tumor suppressor gene regulates the progression of the cell cycle, so its mutation or deletion leads to deregulated cellular proliferation. With respect to TRb, the primary RB1 mutation increases the risk of retinoblastoma and other intracranial tumors complicated malignancies.

Molecular Diagnostics of Trilateral Retinoblastoma

Molecular genetic tests are crucial in the diagnosis of TRB. Verification of the diagnosis is confirmed in the laboratory by testing for RB1 mutations. TRB is almost always associated with germline RB1 mutations, making genetic testing indispensable. A wide range of methods such as Sanger sequencing, next generation sequencing (NGS), and multiplex ligation-dependent probe amplification (MLPA) can be used for mutation analysis.

Along with the analysis of the RB1 mutations, other molecular markers of TRB may be studied in order to further understand the biology of TRB and the disease. For example, certain oncogenes and tumor suppressor genes that are expressed at higher levels can be quantified by qRT-PCR or immunohistochemistry.

Therapeutics Development for Trilateral Retinoblastoma

Chemotherapy: The chemotherapy regimens for TRb usually involve a multi-drug approach which combines different mechanisms related to tumor growth and survival. Commonly used drugs include vincristine, cyclophosphamide, and etoposide; intrathecal methotrexate is given to prevent possible leptomeningeal dissemination. Recent findings suggest that initiating platinum-based chemotherapy with cisplatin early in the course of the disease can enhance survival outcomes.
Targeted Therapy: Research is currently focusing on the use of PARP inhibitors like Olaparib to enhance the effect of cytotoxic agents such as cisplatin. PARP inhibitors also reduce the ability of the tumor cells to repair damaged DNA, leading to increased apoptosis.

Our Services

With our comprehensive molecular and histopathological diagnostics, we offer a unique suite of services in TRb diagnostics development. In therapeutic development, we provide services ranging from preclinical drug development to the design and implementation of preclinical trials.

Diagnostics Development

Karyotype Analysis Service
Omics Analysis Service
Biomarker Development Service
Artificial Intelligence Service
Customized Diagnostics Development

Therapeutic Development

Small Molecule Drug
Cell Therapy
Gene Therapy
Therapeutic Antibody
Therapeutic Peptide
Therapeutic Protein
Customized Therapy Development

Disease Models

SV40 T-antigen (TAg) Transgenic Mouse Models
p107 Double Knockout Models
Rb1 Heterozygous Knockout Mouse Models
TAg-RB Murine Models

Whether it's developing a novel diagnostic assay or advancing a therapeutic candidate, Protheragen provides the scientific expertise and technical capabilities to drive innovation in TRb therapeutic development. If you are interested in our services, please feel free to contact us.

References

de Bloeme, Christiaan M., et al. "Follow-up of cystic pineal glands in retinoblastoma patients does not increase detection of pineal trilateral retinoblastoma." American Journal of Ophthalmology 268 (2024): 199-211.
de Jong, Marcus C., et al. "Trilateral retinoblastoma: a systematic review and meta-analysis." The lancet oncology 15.10 (2014): 1157-1167.