Lacrimal Gland Pleomorphic Adenoma (LGPA, commonly referred to as a mixed tumor) is the most prevalent benign epithelial neoplasm of the lacrimal gland, comprising nearly half of all epithelial tumors in this gland. Protheragen provides a full range of development services for the diagnostics and therapeutics of lacrimal gland pleomorphic adenoma.
Introduction to Lacrimal Gland Pleomorphic Adenoma (LGPA)
Lacrimal gland pleomorphic adenoma (LGPA) is a benign and rare epithelial tumor of the lacrimal gland with slow growth and a painless orbital mass. It is estimated to constitute around 50 percent of all epithelial tumors of the lacrimal gland. LGPA is most commonly diagnosed in middle-aged individuals and is seen more in females. The tumor is made up of an epithelial and myoepithelial portion with glandular, myxoid, or chondroid tissue. Along with exophthalmos, the condition may present with eyelid swelling and reduced vision, which usually trouble the patient for a few years before diagnosis. Despite being benign, LGPA can recur if not treated appropriately and can undergo malignant change.

Fig.1 The entrance points of the main approaches to lacrimal gland pleomorphic adenoma (LGPA). (Horochoski L.,
et al., 2023)
Genetic Alterations Associated with Lacrimal Gland Pleomorphic Adenoma
PLAG1 (Pleomorphic Adenoma Gene 1)
The hallmark of LGPA is the overexpression of PLAG1, which markingly drives the tumor's biphasic nature through proliferation of both epithelial and myxoid cells. In a considerable number of LGPA cases, PLAG1 translocations and gene fusions are recognized.
HMGA2 (High Mobility Group AT-Hook 2)
Some cases of LGPA show overexpression of HMGA2 which assists in tumor growth and differentiation. The alteration of HMGA2 is commonly linked to PLAG1, thereby reinforcing the involvement of these genes in the pathogenesis of LGPA.
Chromosomal Aberrations
Specific chromosomal alterations, particularly gains and losses, define LGPA. In most cases, 9p and 22q are found to be gained, while 1p, 6q, 8q, and 13q are lost. These changes at the genomic level may result in the activation of oncogenes alongside the silencing of tumor suppressor genes fueling the malignant process.
Interleukin-6/Janus Kinase/STAT3 Pathway
Altered expression of the IL-6/JAK/STAT3 signaling pathway is commonly noted in LGPA cases. This pathway enhances cell proliferation, cell survival, and epithelial-mesenchymal transition, all of which are critical to the growth and progression of tumors. Inhibition of this pathway could prove beneficial in the therapeutics of LGPA.
Therapeutics Development for Lacrimal Gland Pleomorphic Adenoma
- STAT3 Pathway Inhibition: Taking into account the overexpression of the STAT3 pathway in both LGPA and CXPA, future therapies working on this pathway may be efficacious. STAT3 inhibitors might decrease tumor growth and restrain the process of malignant transformation.
- CD44 Inhibition: CD44, a surface marker of LGPA, is suggested as a potential therapeutic target by recent studies. Suppressing the expression of CD44 may suppress the corresponding tumor.
- PLAG1 and HMGA2 Gene Therapy: Given that these genes are often overexpressed in LGPA, gene therapy is a possible therapeutic option. Nevertheless, it is still under experimental procedures and needs more studies to confirm proof of concept.
Our Services
Protheragen is at the forefront of Lacrimal Gland Pleomorphic Adenoma therapy development. Our comprehensive services, from diagnostics to preclinical research and customized solutions, position us as a leader in the field.
Diagnostics Development
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
- Customized Diagnostics Development Service
Therapeutic Development
- Small Molecule Drug
- Cell Therapy
- Gene Therapy
- Therapeutic Antibody
- Therapeutic Peptide
- Therapeutic Protein
Disease Models
- PLAG1 Overexpression Mouse Models
- HMGA2 Mutation Pig Models
- PDX Mouse Models
- Chemically Induced Rat Models
Preclinical Research
- Pharmacodynamics Study Services
- Pharmacokinetics Study Services
- Drug Safety Evaluation Services
- Customized Research Services
Protheragen's preclinical research services are designed to accelerate the development of new therapeutics for LGPA. We utilize state-of-the-art animal models to mimic the human disease and evaluate the efficacy, safety, and mechanism of action of novel therapies. If you are interested in our services, please feel free to contact us.
References
- Horochoski, Lucas, Guilherme Warmling Schulz, and Andrei Koerbel. "Lacrimal gland pleomorphic adenoma: a narrative review." Arquivos Brasileiros de Oftalmologia 87.3 (2023): e2022-0057.
- Liu, Rui, et al. "Clinical analysis of 109 cases of lacrimal gland pleomorphic adenoma." International Journal of Ophthalmology 14.12 (2021): 1852.